Pub Date : 2020-01-01DOI: 10.1177/1470320320908186
Damian Cohall, Nkemcho Ojeh, Carlos M Ferrario, O Peter Adams, Marcella Nunez-Smith
Introduction: Low plasma renin activity hypertension is prevalent in Afro-Caribbean persons. Reduced angiotensin converting enzyme 2 activity from the counter angiotensin converting enzyme 2 /angiotensin-(1-7)/Mas receptor axis of the renin angiotensin aldosterone system has been reported in people with pre-hypertension, type 2 diabetes mellitus and chronic renal disease. This study investigates whether an imbalance in the regulatory mechanisms between the pressor arm of the renin angiotensin aldosterone system (angiotensin converting enzyme/angiotensin II/AT1 receptor) and the depressor axis (angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor) predisposes persons of African descent to hypertension.
Methods: In total, 30 normotensives and 30 recently diagnosed hypertensives aged 18-55 of Afro-Caribbean origin who are naïve to antihypertensive treatment will be recruited from public sector polyclinics in Barbados. Demographic and anthropometric data, clinical blood pressure readings, 24-hour urine collections and venous blood samples will be collected. Biological samples will be analysed for renin angiotensin aldosterone system peptide markers using radioimmunoassay.
Conclusion: We describe the design, methods and rationale for the characterization of renin angiotensin aldosterone system mechanisms that may contribute to hypertension predisposition in persons of African descent. Our findings will characterize any imbalance in the counter axes of the renin angiotensin aldosterone system in hypertensive Afro-Caribbeans with a potential view of identifying novel approaches with the use of renin angiotensin aldosterone system and mineralocorticoid blockers to manage the condition.
{"title":"Is hypertension in African-descent populations contributed to by an imbalance in the activities of the ACE2/Ang-(1-7)/Mas and the ACE/Ang II/AT<sub>1</sub> axes?","authors":"Damian Cohall, Nkemcho Ojeh, Carlos M Ferrario, O Peter Adams, Marcella Nunez-Smith","doi":"10.1177/1470320320908186","DOIUrl":"https://doi.org/10.1177/1470320320908186","url":null,"abstract":"<p><strong>Introduction: </strong>Low plasma renin activity hypertension is prevalent in Afro-Caribbean persons. Reduced angiotensin converting enzyme 2 activity from the counter angiotensin converting enzyme 2 /angiotensin-(1-7)/Mas receptor axis of the renin angiotensin aldosterone system has been reported in people with pre-hypertension, type 2 diabetes mellitus and chronic renal disease. This study investigates whether an imbalance in the regulatory mechanisms between the pressor arm of the renin angiotensin aldosterone system (angiotensin converting enzyme/angiotensin II/AT1 receptor) and the depressor axis (angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor) predisposes persons of African descent to hypertension.</p><p><strong>Methods: </strong>In total, 30 normotensives and 30 recently diagnosed hypertensives aged 18-55 of Afro-Caribbean origin who are naïve to antihypertensive treatment will be recruited from public sector polyclinics in Barbados. Demographic and anthropometric data, clinical blood pressure readings, 24-hour urine collections and venous blood samples will be collected. Biological samples will be analysed for renin angiotensin aldosterone system peptide markers using radioimmunoassay.</p><p><strong>Conclusion: </strong>We describe the design, methods and rationale for the characterization of renin angiotensin aldosterone system mechanisms that may contribute to hypertension predisposition in persons of African descent. Our findings will characterize any imbalance in the counter axes of the renin angiotensin aldosterone system in hypertensive Afro-Caribbeans with a potential view of identifying novel approaches with the use of renin angiotensin aldosterone system and mineralocorticoid blockers to manage the condition.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 1","pages":"1470320320908186"},"PeriodicalIF":2.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320320908186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37670189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.1177/1470320320904826
List of reviewers are available in this pdf.
{"title":"Reviewer list","authors":"","doi":"10.1177/1470320320904826","DOIUrl":"https://doi.org/10.1177/1470320320904826","url":null,"abstract":"List of reviewers are available in this pdf.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"109 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80791744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.1177/1470320319900039
Yan Zheng, Jin Huang
Objective: The purpose of the study was to investigate the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.
Methods: A systematic search for relevant literature was performed in MEDLINE, CNKI, and EMBASE. The pooled odds ratios and their corresponding 95% confidence intervals were calculated in STATA 12.0 software.
Results: Seven studies, with a total of 304 patients and 564 controls, qualified for the inclusion in the analysis. There was no significant association between angiotensin-converting enzyme insertion/deletion polymorphism and high-altitude pulmonary edema risk in the total population (DD vs II: odds ratio=1.07, 95% confidence interval 0.52-2.24; DI vs II: odds ratio=1.12, 0.85-1.49; dominant model: odds ratio=1.07, 0.83-1.40; recessive model: odds ratio=0.96, 0.53-1.77). Subgroup analysis according to race also revealed no significant correlation between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.
Conclusions: Our findings suggest that angiotensin-converting enzyme insertion/deletion polymorphism does not contribute to the risk of high-altitude pulmonary edema. Larger, well-designed studies are required to further validate these results.
目的:探讨血管紧张素转换酶基因插入/缺失多态性与高原肺水肿的关系。方法:系统检索MEDLINE、CNKI、EMBASE等相关文献。合并优势比及其对应的95%置信区间在STATA 12.0软件中计算。结果:7项研究，共304例患者和564例对照，符合纳入分析的条件。在总体人群中，血管紧张素转换酶插入/缺失多态性与高原肺水肿风险之间没有显著关联(DD vs II:优势比=1.07,95%可信区间0.52-2.24;DI vs II:优势比=1.12,0.85-1.49;优势模型:优势比=1.07,0.83-1.40;隐性模型:优势比=0.96,0.53-1.77)。不同种族的亚组分析也显示血管紧张素转换酶基因插入/缺失多态性与高原肺水肿无显著相关性。结论:我们的研究结果表明，血管紧张素转换酶插入/缺失多态性与高原肺水肿的风险无关。需要更大规模、设计良好的研究来进一步验证这些结果。
{"title":"Angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema: An updated meta-analysis.","authors":"Yan Zheng, Jin Huang","doi":"10.1177/1470320319900039","DOIUrl":"https://doi.org/10.1177/1470320319900039","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of the study was to investigate the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.</p><p><strong>Methods: </strong>A systematic search for relevant literature was performed in MEDLINE, CNKI, and EMBASE. The pooled odds ratios and their corresponding 95% confidence intervals were calculated in STATA 12.0 software.</p><p><strong>Results: </strong>Seven studies, with a total of 304 patients and 564 controls, qualified for the inclusion in the analysis. There was no significant association between angiotensin-converting enzyme insertion/deletion polymorphism and high-altitude pulmonary edema risk in the total population (DD vs II: odds ratio=1.07, 95% confidence interval 0.52-2.24; DI vs II: odds ratio=1.12, 0.85-1.49; dominant model: odds ratio=1.07, 0.83-1.40; recessive model: odds ratio=0.96, 0.53-1.77). Subgroup analysis according to race also revealed no significant correlation between angiotensin-converting enzyme gene insertion/deletion polymorphism and high-altitude pulmonary edema.</p><p><strong>Conclusions: </strong>Our findings suggest that angiotensin-converting enzyme insertion/deletion polymorphism does not contribute to the risk of high-altitude pulmonary edema. Larger, well-designed studies are required to further validate these results.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"21 1","pages":"1470320319900039"},"PeriodicalIF":2.9,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320319900039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37684183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.1177/1470320319881932
Zhen Cheng, Zhiwei Liu
Objective: The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer. Methods: We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59). Conclusion: Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.
目的:肾素-血管紧张素系统基因与结直肠癌的进展有关。然而，这一角色的细节仍存在争议。我们进行了一项荟萃分析，以调查肾素-血管紧张素系统基因多态性与结直肠癌之间的相关性。方法:我们从PubMed和Embase检索相关研究。随后，使用固定或随机效应模型计算95%置信区间(ci)的合并优势比(ORs)。结果:我们确定了6项血管紧张素转换酶插入/缺失(I/D)多态性研究和2项血管紧张素原M235T多态性研究。在总体人群中，血管紧张素转换酶I/D多态性与结直肠癌风险无显著相关性(DD vs II: OR 0.77, 95% CI 0.39-1.50;DI vs. II: OR 1.05, 95% CI 0.85-1.30;优势模型:OR 0.94, 95% CI 0.68-1.31;隐性模型:OR 1.01, 95% CI 0.80-1.27)。同样，血管紧张素原M235T多态性与结直肠癌风险无关(TT vs. MM: OR 1.38, 95% CI 0.52-3.67;TM vs. MM: OR 1.19, 95% CI 0.96-1.47;优势模型:OR 1.28, 95% CI 0.77-2.14;隐性模型:OR 1.17, 95% CI 0.53-2.59)。结论:血管紧张素转换酶I/D和血管紧张素原M235T多态性与结直肠癌的相关性不大。
{"title":"Renin–angiotensin system gene polymorphisms and colorectal cancer risk: a meta-analysis","authors":"Zhen Cheng, Zhiwei Liu","doi":"10.1177/1470320319881932","DOIUrl":"https://doi.org/10.1177/1470320319881932","url":null,"abstract":"Objective: The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer. Methods: We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59). Conclusion: Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"7 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88790457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.1177/1470320319889415
J. Ferreira, P. Rossignol, F. Zannad
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). The interplay between the renin-angiotensin-aldosterone system (RAAS) and kidneys in patients with heart failure (HF) can lead to highly complex and challenging clinical scenarios. Among these scenarios, worsening renal function (WRF) and/or hydro-electrolytic alterations (hyperkalemia in particular) often raise clinicians’ awareness leading to downstream decisions (e.g. change in medications and/or its dosages), which can have consequences for the patients.1 It should, nonetheless, be noted that WRF (a major determinant of adverse outcomes in HF patients) may be of multifactorial origin and the RAAS inhibitors (RAASi) are one of its multiple causes. This is thought to occur because RAAS activation in HF leads to glomerular efferent arteriolar vasoconstriction that preserves glomerular filtration (in the face of a fall in glomerular perfusion pressure caused by HF). By reducing this neurohormonal activation, RAAS blockers can reduce the glomerular perfusion pressure (reducing systemic arterial and glomerular afferent arteriolar pressure while also preventing the compensatory efferent arteriolar constriction) and cause WRF.2 However, used chronically, RAASi treatment may attenuate renal function deterioration, suggesting an initial creatinine rise may not be clinically relevant in certain populations.3 Increment in serum creatinine/WRF occurring in the setting of decongestion or titration of neurohormonal antagonists is also commonly encountered, primarily as a result of the effects of loop diuretics and/or of RAASi on renal hemodynamics. Recent data showed that when HF medications (i.e. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs), β-blockers and diuretics) were held for 48 hours, serum creatinine decreased but natriuretic peptides and cardiac volumes increased.4 These data support the concept that serum creatinine increases and WRF should not be evaluated in isolation but rather considered in the context of the whole clinical scenario: not all increases in serum creatinine adversely affect prognosis. For example, a meta-analysis showed that WRF in patients with HF with reduced ejection fraction (HFrEF) randomized to an RAASi therapy was associated with lower mortality than WRF on placebo.5 It should be emphasized that RAASi have convincing evidence of benefit on prolonging survival and reducing morbidity in patients with HFrEF, and both United States and European guidelines give a Class I, Level of Evidence A recommendation for their
{"title":"Renin-angiotensin-aldosterone system and kidney interactions in heart failure","authors":"J. Ferreira, P. Rossignol, F. Zannad","doi":"10.1177/1470320319889415","DOIUrl":"https://doi.org/10.1177/1470320319889415","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). The interplay between the renin-angiotensin-aldosterone system (RAAS) and kidneys in patients with heart failure (HF) can lead to highly complex and challenging clinical scenarios. Among these scenarios, worsening renal function (WRF) and/or hydro-electrolytic alterations (hyperkalemia in particular) often raise clinicians’ awareness leading to downstream decisions (e.g. change in medications and/or its dosages), which can have consequences for the patients.1 It should, nonetheless, be noted that WRF (a major determinant of adverse outcomes in HF patients) may be of multifactorial origin and the RAAS inhibitors (RAASi) are one of its multiple causes. This is thought to occur because RAAS activation in HF leads to glomerular efferent arteriolar vasoconstriction that preserves glomerular filtration (in the face of a fall in glomerular perfusion pressure caused by HF). By reducing this neurohormonal activation, RAAS blockers can reduce the glomerular perfusion pressure (reducing systemic arterial and glomerular afferent arteriolar pressure while also preventing the compensatory efferent arteriolar constriction) and cause WRF.2 However, used chronically, RAASi treatment may attenuate renal function deterioration, suggesting an initial creatinine rise may not be clinically relevant in certain populations.3 Increment in serum creatinine/WRF occurring in the setting of decongestion or titration of neurohormonal antagonists is also commonly encountered, primarily as a result of the effects of loop diuretics and/or of RAASi on renal hemodynamics. Recent data showed that when HF medications (i.e. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs), β-blockers and diuretics) were held for 48 hours, serum creatinine decreased but natriuretic peptides and cardiac volumes increased.4 These data support the concept that serum creatinine increases and WRF should not be evaluated in isolation but rather considered in the context of the whole clinical scenario: not all increases in serum creatinine adversely affect prognosis. For example, a meta-analysis showed that WRF in patients with HF with reduced ejection fraction (HFrEF) randomized to an RAASi therapy was associated with lower mortality than WRF on placebo.5 It should be emphasized that RAASi have convincing evidence of benefit on prolonging survival and reducing morbidity in patients with HFrEF, and both United States and European guidelines give a Class I, Level of Evidence A recommendation for their ","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"295 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74962008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-01DOI: 10.1177/1470320319882656
A. R. Silva, A. Martini, G. Canto, E. Guerra, F. Neves
Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (p=0.0006) in all individuals, and to 0.86 (p=0.005) in patients with RD and to 0.91 (p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.
{"title":"Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis","authors":"A. R. Silva, A. Martini, G. Canto, E. Guerra, F. Neves","doi":"10.1177/1470320319882656","DOIUrl":"https://doi.org/10.1177/1470320319882656","url":null,"abstract":"Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (p=0.0006) in all individuals, and to 0.86 (p=0.005) in patients with RD and to 0.91 (p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"2012 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83371030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Increased circulating level of plasminogen activator inhibitor-1 (PAI-1) is associated with menopausal oestrogen deficiency. We therefore hypothesised that the combined oral contraceptive (COC) with spironolactone (SPL) improves insulin resistance (IR) in ovariectomised (OVX) rats by reducing circulating PAI-1.
Methods: Twelve-week-old female Wistar rats were divided into sham-operated (SHM), OVX, OVX+SPL (0.25 mg/kg), COC (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) and OVX+COC+SPL rats treated with COC and SPL daily for eight weeks. IR was assessed by homeostatic model assessment of IR (HOMA-IR).
Results: Data showed that OVX rats had a higher HOMA-IR value that is associated with increased visceral adiposity, triglycerides (TG), total cholesterol/high-density lipoprotein cholesterol (HDL-C), TG/HDL-C, plasma insulin, GSK-3, corticosterone and decreased 17β-oestradiol. However, these effects were attenuated in OVX+COC, OVX+SPL and OVX+COC+SPL rats compared to OVX rats. OVX rats had lower PAI-1 than SHM rats, whereas the beneficial effect on IR and other parameters by COC or SPL was accompanied with increased PAI-1. Improvement of IR and other parameters with combined COC and SPL in OVX rats was accompanied with reduced PAI-1.
Conclusion: Taken together, COC or SPL improves IR independent of PAI-1, whereas a combination of COC and SPL in OVX rats ameliorates IR in a PAI-1-dependent manner.
{"title":"Combined but not single treatment with ethinylestradiol/levonorgestrel and spironolactone reduces plasminogen activator inhibitor-1 in insulin-resistant ovariectomised rats.","authors":"Adeyanju Oluwaseun Aremu, Dibia Chinaza Lilian, Soladoye Ayodele Olufemi, Olatunji Lawrence Aderemi","doi":"10.1177/1470320319895933","DOIUrl":"https://doi.org/10.1177/1470320319895933","url":null,"abstract":"<p><strong>Objective: </strong>Increased circulating level of plasminogen activator inhibitor-1 (PAI-1) is associated with menopausal oestrogen deficiency. We therefore hypothesised that the combined oral contraceptive (COC) with spironolactone (SPL) improves insulin resistance (IR) in ovariectomised (OVX) rats by reducing circulating PAI-1.</p><p><strong>Methods: </strong>Twelve-week-old female Wistar rats were divided into sham-operated (SHM), OVX, OVX+SPL (0.25 mg/kg), COC (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) and OVX+COC+SPL rats treated with COC and SPL daily for eight weeks. IR was assessed by homeostatic model assessment of IR (HOMA-IR).</p><p><strong>Results: </strong>Data showed that OVX rats had a higher HOMA-IR value that is associated with increased visceral adiposity, triglycerides (TG), total cholesterol/high-density lipoprotein cholesterol (HDL-C), TG/HDL-C, plasma insulin, GSK-3, corticosterone and decreased 17β-oestradiol. However, these effects were attenuated in OVX+COC, OVX+SPL and OVX+COC+SPL rats compared to OVX rats. OVX rats had lower PAI-1 than SHM rats, whereas the beneficial effect on IR and other parameters by COC or SPL was accompanied with increased PAI-1. Improvement of IR and other parameters with combined COC and SPL in OVX rats was accompanied with reduced PAI-1.</p><p><strong>Conclusion: </strong>Taken together, COC or SPL improves IR independent of PAI-1, whereas a combination of COC and SPL in OVX rats ameliorates IR in a PAI-1-dependent manner.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"20 4","pages":"1470320319895933"},"PeriodicalIF":2.9,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1470320319895933","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37473777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-09DOI: 10.5772/intechopen.88052
K. Satué, A. Muñoz
In women and laboratory animals, local and circulating components of the renin-angiotensin-aldosterone system (RAAS) are related to specific reproductive functions that occur during the estrous cycle, such as folliculogenesis, ovulation, corpus luteum development, and steroidogenesis. Also, in pregnant females of these species, maternal cardiovascular and renal systems undergo intense modifications, with the aim of matching the increased energy requirements of the fetus and fetoplacental unit. Some of these changes can be the origin, and others the consequence of a new endocrine environment. The fetus and the placenta induce endocrine changes, with modifications in the protein, lipid, carbohydrate, and mineral metabolism, together with simultaneous cardiovascular changes derived from the uterine growth and its content. The participation of RAAS during this period is of vital importance to regulate these cardiovascular, hemodynamic, hematological, and metabolic adjustments imposed by pregnancy because they will have a direct influence on the correct development and viability of the fetus. In mares, our research team has been investigating the changes of RAAS in mares during the estral cycle and during pregnancy, and these results are presented in the current chapter, comparing with the data previously reported for women and laboratory animals.
{"title":"Scientific Evidences Supporting the Activation of the Renin-Angiotensin-Aldosterone System during Estral Cycle and Pregnancy in Mares","authors":"K. Satué, A. Muñoz","doi":"10.5772/intechopen.88052","DOIUrl":"https://doi.org/10.5772/intechopen.88052","url":null,"abstract":"In women and laboratory animals, local and circulating components of the renin-angiotensin-aldosterone system (RAAS) are related to specific reproductive functions that occur during the estrous cycle, such as folliculogenesis, ovulation, corpus luteum development, and steroidogenesis. Also, in pregnant females of these species, maternal cardiovascular and renal systems undergo intense modifications, with the aim of matching the increased energy requirements of the fetus and fetoplacental unit. Some of these changes can be the origin, and others the consequence of a new endocrine environment. The fetus and the placenta induce endocrine changes, with modifications in the protein, lipid, carbohydrate, and mineral metabolism, together with simultaneous cardiovascular changes derived from the uterine growth and its content. The participation of RAAS during this period is of vital importance to regulate these cardiovascular, hemodynamic, hematological, and metabolic adjustments imposed by pregnancy because they will have a direct influence on the correct development and viability of the fetus. In mares, our research team has been investigating the changes of RAAS in mares during the estral cycle and during pregnancy, and these results are presented in the current chapter, comparing with the data previously reported for women and laboratory animals.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"7 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82343637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-22DOI: 10.5772/INTECHOPEN.88054
X. Li, A. Leite, Xu Chen, Chunling Zhao, Xiaowen Zheng, Jianfeng Zhang, J. Zhuo
The kidney plays a fundamental role in the physiological regulation of basal blood pressure and the development of hypertension. Although the mechanisms underlying hypertension are very complex, the renin-angiotensin system (RAS) in the kidney, especially intratubular and intracellular RAS, undoubtedly plays a critical role in maintaining basal blood pressure homeostasis and the development of angiotensin II (ANG II)-dependent hypertension. In the proximal tubules, ANG II activates two G protein-coupled receptors, AT 1 and AT 2 , to exert powerful effects to regulate proximal tubular sodium and fluid reabsorption by activating cell surface as well as intracellular AT 1 receptors. Increased production and actions of ANG II in the proximal tubules may cause salt and fluid retention, impair the pressure-natriuresis response, and consequently increase blood pressure in hypertension. The objectives of this chapter are to critically review and discuss our current understanding of intratubular and intracellular RAS in the kidney, and their contributions to basal blood pressure homeostasis and the development of ANG II-dependent hypertension. The new knowledge will likely help uncover novel renal mechanisms of hypertension, and develop kidney- or proximal tubule-specific strategies or drugs to prevent and treat hypertension in humans.
{"title":"The Intratubular and Intracrine Renin-Angiotensin System in the Proximal Tubules of the Kidney and Its Roles in Angiotensin II-Induced Hypertension","authors":"X. Li, A. Leite, Xu Chen, Chunling Zhao, Xiaowen Zheng, Jianfeng Zhang, J. Zhuo","doi":"10.5772/INTECHOPEN.88054","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.88054","url":null,"abstract":"The kidney plays a fundamental role in the physiological regulation of basal blood pressure and the development of hypertension. Although the mechanisms underlying hypertension are very complex, the renin-angiotensin system (RAS) in the kidney, especially intratubular and intracellular RAS, undoubtedly plays a critical role in maintaining basal blood pressure homeostasis and the development of angiotensin II (ANG II)-dependent hypertension. In the proximal tubules, ANG II activates two G protein-coupled receptors, AT 1 and AT 2 , to exert powerful effects to regulate proximal tubular sodium and fluid reabsorption by activating cell surface as well as intracellular AT 1 receptors. Increased production and actions of ANG II in the proximal tubules may cause salt and fluid retention, impair the pressure-natriuresis response, and consequently increase blood pressure in hypertension. The objectives of this chapter are to critically review and discuss our current understanding of intratubular and intracellular RAS in the kidney, and their contributions to basal blood pressure homeostasis and the development of ANG II-dependent hypertension. The new knowledge will likely help uncover novel renal mechanisms of hypertension, and develop kidney- or proximal tubule-specific strategies or drugs to prevent and treat hypertension in humans.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"31 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90184954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-25DOI: 10.5772/INTECHOPEN.88170
M. Ciocoiu, Iris Bararu-Bojan, M. Vlădeanu, C. Bădescu
Since its discovery in 1898, the renin-angiotensin-aldosterone system (RAAS) has been intensely studied in the medical community, which led to important breakthroughs concerning the treatment of heart diseases. The main role of RAAS is to maintain the circulatory homeostasis, by maintaining the fluid volume. Angiotensin II (ANG II) can act on two receptors: angiotensin type 1 and angiotensin type 2 (AT1R and AT2R). The effect of AT1R consists in increased sodium retention, promotes vasoconstriction (mostly on the efferent arteriole), induces sympathetic nervous system activity, determines thirst and promotes the release of aldosterone. Abnormal activation of RAAS will determine hypertension and cardiac hypertrophy that may lead to heart failure. This is the reason why the pharmacological inhibition of this system has proven to induce such a beneficial effect in cardiovascular diseases such as hypertension and congestive heart failure. Later studies of patients with coronary artery disease revealed that angiotensin-converting enzyme (ACE) gene is also involved in the process of atherosclerosis and those mutations in its gene account for an increased susceptibility to severe acute coronary events. The most common ACE gene mutation is represented by deletions and insertions in the 16th intron (presence or absence of the 287-bp Alu repeat sequence), resulting in three possible genotypes, identified by the length of the fragments: II (490 bp), ID (490, 190 bp) and DD (190 bp). Scientific evidence suggests that the D allele plays a major role in the determination of coronary artery disease. The next step would be to develop new treatment strategies according to the genetic background of each patient.
{"title":"The Renin-Angiotensin-Aldosterone System: Genomics, Proteomics and Therapeutic Implications","authors":"M. Ciocoiu, Iris Bararu-Bojan, M. Vlădeanu, C. Bădescu","doi":"10.5772/INTECHOPEN.88170","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.88170","url":null,"abstract":"Since its discovery in 1898, the renin-angiotensin-aldosterone system (RAAS) has been intensely studied in the medical community, which led to important breakthroughs concerning the treatment of heart diseases. The main role of RAAS is to maintain the circulatory homeostasis, by maintaining the fluid volume. Angiotensin II (ANG II) can act on two receptors: angiotensin type 1 and angiotensin type 2 (AT1R and AT2R). The effect of AT1R consists in increased sodium retention, promotes vasoconstriction (mostly on the efferent arteriole), induces sympathetic nervous system activity, determines thirst and promotes the release of aldosterone. Abnormal activation of RAAS will determine hypertension and cardiac hypertrophy that may lead to heart failure. This is the reason why the pharmacological inhibition of this system has proven to induce such a beneficial effect in cardiovascular diseases such as hypertension and congestive heart failure. Later studies of patients with coronary artery disease revealed that angiotensin-converting enzyme (ACE) gene is also involved in the process of atherosclerosis and those mutations in its gene account for an increased susceptibility to severe acute coronary events. The most common ACE gene mutation is represented by deletions and insertions in the 16th intron (presence or absence of the 287-bp Alu repeat sequence), resulting in three possible genotypes, identified by the length of the fragments: II (490 bp), ID (490, 190 bp) and DD (190 bp). Scientific evidence suggests that the D allele plays a major role in the determination of coronary artery disease. The next step would be to develop new treatment strategies according to the genetic background of each patient.","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":"251 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89056169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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