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

Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must be explored to understand how ACE inhibition may impact our ability to clear infections or malignancy, particularly in the wake of the coronavirus (SARS-CoV2) pandemic and as antibiotic resistance grows. Patients using ACE inhibitors may be more at risk of postsurgical complications as ACE inhibition in human neutrophils results in decreased ROS and phagocytosis whilst angiotensin receptor blockers (ARBs) have no effect. In contrast, ACE is also elevated in certain autoimmune diseases such as rheumatoid arthritis and lupus, and its inhibition benefits patient outcome where inflammatory immune cells are overactive. Although the ACE autoimmune landscape is changing, some studies have conflicting results and require further input. This review seeks to highlight the need for further research covering ACE inhibitor therapeutics and their potential role in improving autoimmune conditions, cancer, or how they may contribute to immunocompromise during infection and neurodegenerative diseases. Understanding ACE inhibition in immune cells is a developing field that will alter how ACE inhibitors are designed in future and aid in developing therapeutic interventions.

Backgrounds: Estrogen replacement therapy (ERT) and hypertension may influence females' renin-angiotensin system (RAS) and its components. The angiotensin II (Ang II) type 1 receptor (AT1R) antagonist (losartan) may promote renal blood flow (RBF), and it is widely used in the clinic to control hypertension. The main objective of this study was the effects of estradiol or induced hypertension on RBF response to Ang II in losartan-treated ovariectomized (OVX) rats.

Methods: Two groups of OVX rats were treated with placebo (group 1) and estradiol (group 2) for period of four weeks, and another group of OVX rats was subjected to induce hypertension by two-kidney one clip (2K1C) model (group 3). All the groups were subjected to the surgical procedure under anesthesia, and AT1R was blocked by losartan. RBF and renal vascular resistance (RVR) responses to Ang II administration were determined and compared.

Results: Mean arterial (MAP) and renal perfusion (RPP) pressures in group 3 and uterus weight (UT) in group 2 were significantly more than other groups (P < 0.05). Ang II infusion resulted in dose-related percentage change increase in RBF and decrease in RVR. However, these responses in the OVX-estradiol and OVX-hypertensive rats were significantly lower than in the OVX-control group (P < 0.05). For instance, at the dose of 1000 ng/kg/min of Ang II administration, the percentage change of RBF was 45.1 ± 10.4%, 17.9 ± 2.3%, and 16.7 ± 4.7% in the groups of 1 to 3, respectively.

Conclusion: Losartan prescription in some conditions such as hypertension or ERT could worsen RBF and RVR responses to Ang II.

Background: In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system.

Methods: Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test.

Results: Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats (P < 0.05). After castration, captopril decreased serum Ang II concentration (P < 0.05); in female rats, icatibant increased serum Ang II concentration (P < 0.05). Captopril increased serum bradykinin concentration (P < 0.05); in male rats, icatibant decreased serum bradykinin concentration (P < 0.05). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration (P < 0.05). Icatibant decreased urine DPD/Cr in male rats (P < 0.05) and increased osteocalcin concentration in female rats (P < 0.05). Captopril increased cancellous BMD in castrated hypertensive rats (P < 0.05), and icatibant further increased cancellous BMD (P < 0.05), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength (P < 0.05), and icatibant further improved it (P < 0.05).

Conclusion: ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.

We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis. This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model. The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population (TT vs. MM: OR = 1.28, 95%CI = 0.80 - 2.04; TM vs. MM: OR = 0.90, 95%CI = 0.53 - 1.52; recessive model: OR = 1.13, 95%CI = 0.83 - 1.52; dominant model: OR = 0.93, 95%CI = 0.55 - 1.57). Subgroup analysis by ethnicity, cancer type, and study quality for the relationship between the AGT M235T polymorphism and cancer risk showed no significant association. According to findings in the present meta-analysis, AGT M235T polymorphism may not be related to cancer susceptibility.

The COVID-19 pandemic has resulted in an unprecedented impact on global health, economy, and way of life. SARS-CoV-2, the virus responsible for the disease, utilizes the ACE2 receptor found on host cells to mediate entry, replication, and infection. Numerous studies have elucidated the presence of many components of the renin-angiotensin-aldosterone system (RAAS) in the eye, including the ACE2 receptor. Considering this, and the anatomical vulnerability that the exposed ocular surface offers with its interconnectedness to the respiratory system, there is a theoretical risk of pathogen entry from the ocular route as well as the development of COVID-19-associated eye disease. Despite this, the actual epidemiological data demonstrates low ocular symptoms, possibly due to differing ACE2 receptor expression across age, ethnicity, and sex coupled with the protective properties of tears. We summarize the current literature on ocular RAAS with specific focus on the ACE2 receptor and its interplay with the SARS-CoV-2 virus.

Objective: Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. The purpose of this study was to investigate the role and mechanism of tolvaptan (TOL) in CI-AKI.

Methods: 24 Wistar male rats were randomly divided into 4 groups (n = 6). And a rat model of CI-AKI was established. Then, the blood and urine of rats in each group were collected to detect relevant parameters. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues.

Results: TOL could significantly reduce the serum level of urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decrease serum Cys-C and urine KIM-1 in CI-AKI rats. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. In addition, TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. After the pretreatment of TOL, the expression of proapoptotic proteins cleaved-caspase 3 and BAX, as well as mitochondrial fusion proteins DRP1 and MFN2 was downregulated, while the expression of Bcl-2 and PINK1 was upregulated in the kidney tissue of CI-AKI rats. Further, TOL could activate the Nrf2 signaling pathway, and the Nrf2 inhibitor ML385 reversed the effect of TOL on CI-AKI.

Conclusion: TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis.

Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.