Journal of the Renin-Angiotensin-Aldosterone System最新文献

Introduction: The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people.

Results: The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups.

Conclusion: Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.

Introduction: Excessive intake of fructose increases serum uric acid concentration. Hyperuricemia induces a negative effect on atherosclerosis and inflammation. Hyperuricemia is common in patients with arterial hypertension. Several antihypertensive drugs including diuretics increase serum uric acid concentration. In contrast, the angiotensin II receptor antagonist (ARB) losartan was found to lower serum uric acid though it may increase renal excretion while other ARBs showed mostly a neutral effect. In this study, effects of two AT1 receptor antagonists losartan and eprosartan on serum uric acid changes induced by oral fructose load were directly compared.

Methods: The randomized, crossover, head-to-head comparative study comprised 16 ambulatory patients (mean age 64.5 ± 9.8 years). The patients fulfilled AHA/NHLBI 2005 criteria of metabolic syndrome. A daily single morning dose of each study drug (50 mg of losartan or 600 mg of eprosartan) was given during two 3-month periods in a random order separated by 2-week washout time. The oral fructose tolerance test (OFTT) was performed at baseline and after each two 3-onth treatment periods. Before and during OFTT, urine excretion of uric acid and creatinine was assessed in the first morning portion of urine. Blood samples for the measurement of serum uric acid and lipids were taken at baseline and 30, 60, and 120 minutes after oral intake of 75 g of fructose.

Results: After 3-month treatment with eprosartan and losartan, both systolic and diastolic blood pressure decreased significantly and to a similar extent. After the treatment, serum uric acid and its baseline and postfructose urine excretion were unchanged. No significant changes of plasma lipids before and after OFTT were observed throughout the study.

Conclusions: The study showed that in patients with hypertension and metabolic syndrome, both losartan and eprosartan have a neutral effect on fasting and postfructose load serum uric acid concentration and its urinary excretion. This trial is registered with NCT04954560.

Materials and methods: Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks.

Results: The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group.

Conclusions: Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.

Results: Prolonged exposure to palmitate increased the expression of ACE and AngII type 1 receptor (ATR1) and decreased the ACE2 expression, which was partly offset by berberine. In ob/ob mice, berberine increased in tolerance to glucose, improved abnormal β-cell and α-cell distributions, upregulated ACE2 expression, and decreased autophagosomes and the expression of LC3 and SQSTM1/p62. Autophagosomes and expression of LC3 and SQSTM1/p62 were increased in ACE2KO mice.

Conclusions: We demonstrated that berberine may improve the pancreatic islet function by regulating local RAS-mediated autophagy under metabolic stress.

Objective: To investigate the proliferation effect of aldosterone on renal tubular epithelial cells in vivo and in vitro.

Methods: Thirty-two male C57BL/6J mice (20-22 g) were divided randomly into four groups: sham, unilateral nephrectomy (UN), unilateral nephrectomy plus aldosterone infusion (UA), and UA plus eplerenone (UAE). The kidneys were removed 6 weeks after treatment. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry and western blotting. Human kidney proximal tubular epithelial (HK2) and mouse distal convoluted tubule (mDCT) cell lines were stimulated by aldosterone (0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L) in vitro. Cells were collected after 3, 6, 12, 24, 36, and 48 h, and proliferation of each group detected by western blotting, flow cytometry, live imaging, and the MTT assay. In addition, mDCT cells were costimulated with a medium containing a final concentration of 161 mmol/L Na⁺ and different concentrations of aldosterone, and the number of cells and cellular DNA content was measured by the MTT assay and flow cytometry.

Results: Aldosterone could induce a significant increase in the number of PCNA-positive cells in mouse kidneys accompanied by increased deposition of collagen fibers. Eplerenone could inhibit aldosterone-induced cell proliferation and collagen deposition. HK2 cells and mDCT cells administered different concentrations, and different times of aldosterone stimulation failed to cause cell proliferation, and costimulation of aldosterone and salt did not cause proliferation changes in mDCT cells.

Conclusions: Aldosterone perfusion can induce proliferation of mouse kidney cells in vivo, and eplerenone can inhibit this change, but aldosterone stimulates HK2 cells and mDCT in vitro without causing their proliferation.

Materials and methods: Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically.

Results: Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens.

Conclusions: Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.

The Na⁺/H⁺ ion exchanger (NHE) pumps Na⁺ inward the cell and H⁺ ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H⁺ ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H⁺ ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H⁺ ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.