Role Of Renin-angiotensin System Inhibitors Research Articles

Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08–3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928–6.451, p < 0.001 and HR = 1.8; 95%CI 0.983–3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92–10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21–0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24–1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07–1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

“May You Live in Interesting Times”: Incorporation of COVID‐19 Topics in Pharmacology Instruction in Pharm.D. Curriculum

COVID‐19 pandemic created many challenges for education enterprise, but also presented several opportunities, including new content developments and clear basic science applicability in health professions. We incorporated several COVID‐19‐related topics in pharmacology content taught throughout the Pharm.D. curriculum and analyzed student performance on related assignments.In first professional year class, we created an active learning exercise in Principles of Drug Action course about pharmacology of glucocorticoids that included recently published articles about the use of dexamethasone in severely‐ill COVID‐19 patients. Students completed an open‐book group assignment containing open‐ended questions on glucocorticoid pharmacology and COVID‐19 treatment. They mastered the material with average scores of 89.06% on questions related to general glucocorticoid pharmacology and 98.21% on COVID‐related glucocorticoid use questions. In professional year two, we created an active learning practice opportunity for Integrated Pharmacotherapy: Cardiology class about the role of renin‐angiotensin system (RAS) pathways and their inhibition in COVID‐19. Readings that summarized recent controversies about the role of RAS inhibitors in COVID‐19 were chosen. Students worked in groups on open‐ended questions about general pharmacology of RAS inhibitors and their proposed and observed effects on COVID‐19. Student scores for general pharmacology of RAS inhibitors questions and RAS inhibitors’ effects on COVID‐19 were similar in this activity, with the averages of 88.99% and 87.17%, respectively. Over the semester students demonstrated a trend towards improvement in their RAS pharmacology performance on closed‐book assessments, which increased from 70.3% on the first test to the average of 84.6% on subsequent exams, however, the observed difference was not statistically significant. Finally, antiviral pharmacology lecture in Integrated Pharmacotherapy: Infectious Disease course presented to third professional year students included COVID‐related content. We did not test students on COVID‐related pharmacology content specifically in this class and their overall performance on antiviral drugs pharmacology exam questions was similar to last year's class performance (79.73% vs. 76.79%).Our observations indicate that additional practice opportunities that demonstrate clear clinical relevance of pharmacology content can positively affect student performance as evidenced by high average scores on reported assessments. These class activities may promote our students commitment to lifelong learning.

The Effect of Renin-Angiotensin System Inhibitors on the Recurrence of Atrial Fibrillation After Catheter Ablation.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Renin-angiotensin system (RAS) inhibitors were reported to modify the arrhythmia substrate and reverse atrial remodeling. However, the role of RAS inhibitors on AF recurrence after catheter ablation remains much more controversial. In this study, a meta-analysis was performed to explore the effect of RAS inhibitors on AF recurrence after catheter ablation.We searched PubMed, Cochrane Library, EMBASE, and Web of Science for all articles published up to July 2019 on the effect of RAS inhibitors on AF recurrence rate after ablation. We used the random-effects model to estimate the odds ratios (ORs) and confidence intervals (CI). The I2 statistic was used to evaluate statistical heterogeneity. A two-tailed P value of <0.05 was considered statistically significant. Results were further analyzed by subgroup according to the type of study design.We included 13 studies, including 3661 patients with AF, in this analysis, of which 4 were randomized controlled trials (RCTs) and the others were cohort studies. Overall, treatment with RAS inhibitors showed a significant reduction of AF recurrence after catheter ablation (OR, 0.61; 95% CI, 0.45-0.82). Additionally, both the RCT (OR, 0.35; 95% CI, 0.24-0.49) and non-RCT (OR, 0.76; 95% CI, 0.57-1.00) groups demonstrated that RAS inhibitors could reduce the AF recurrence rate after catheter ablation in the subgroup analysis.Our meta-analysis suggests that RAS inhibitors had significant benefit in reducing the recurrence rate of AF after catheter ablation.

Is there any role of renin-angiotensin system inhibitors in modulating inflammatory bowel disease outcome?

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been associated with improved outcomes in inflammatory bowel disease. We aimed to investigate any possible effect of antihypertensive medications on inflammatory bowel disease course. One hundred and fifty inflammatory bowel disease patients with hypertension were compared using a 1:1 ratio with age- and gender-matched control patients with inflammatory bowel disease. The class of antihypertensive medication, traditional risk factors for atherosclerosis, inflammatory bowel disease characteristics, and history (surgery, hospitalizations, and treatment) were retrospectively analyzed. Of 150 (44.7% Crohn's disease) patients with hypertension, 46.7% were on angiotensin receptor blockers, 30.6% on angiotensin-converting enzyme inhibitors, 40% on β-blockers, and 40.7% on calcium channel blockers. Univariate analysis revealed significantly higher rates of traditional risk factors for atherosclerosis among antihypertensive users. When analyzing by class of antihypertensive medication, angiotensin receptor blockers were significantly associated with milder course as indicated by less frequent immunomodulator (P = 0.039) and steroid use (P = 0.041). Rates of lifetime steroids were statistically significantly lower among angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio = 1.191, 95% confidence interval, 1.005-1.411). After adjustment with confounding factors, only angiotensin receptor blockers were associated with milder inflammatory bowel disease course (P = 0.037) and lower rates of immunomodulator use (P = 0.038). Our study suggests a possible protective effect of angiotensin receptor blockers on overall inflammatory bowel disease course by targeting the renin-angiotensin system. Their effect on inflammatory bowel disease needs to be studied in larger cohorts.

Systematic review of the role of renin-angiotensin system inhibitors in late studies on Covid-19: A new challenge overcome?

A role for the renin-angiotensin-aldosterone-system in Severe Acute Respiratory Syndrome-Coronavirus-2 infection and in the development of COronaVIrus Disease-19 disease has generated remarkable concerns among physicians and patients. Even though a suggestive pathophysiological link between renin-angiotensin-aldosterone-system and the virus has been proposed, its pathogenic role remains very difficult to be defined. Although COronaVIrus Disease-19 targets preferentially older people with high prevalence of hypertension and extensive use of renin-angiotensin-aldosterone-system inhibitors, an independent role for hypertension and its therapies is not defined. In this article, we scrutinize evidence from the most representative available studies in which the potential role of renin-angiotensin system inhibitors, specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, was evaluated in the COronaVIrus Disease-19 disease course, with regard to severity of the disease and mortality. We conclude that at this time, the overall available evidence fails to support a pathogenetic speaks against any harmful role for of renin-angiotensin-aldosterone-system inhibitors in COronaVIrus Disease-19. Consequently, we conclude that treatment with renin-angiotensin-aldosterone-system inhibitors should not be discontinued and, therefore, these therapies should not be interrupted.

Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

Renin-angiotensin system inhibitor attenuates oxidative stress induced human coronary artery endothelial cell dysfunction via the PI3K/AKT/mTOR pathway.

IntroductionThe renin-angiotensin system is associated with blood pressure regulation, inflammation, oxidative stress and insulin resistance. It can decrease intracellular oxidative stress. Stimulation with H2O2 leads to increased oxidative stress and activation of the AKT/mTOR pathway. However, the role of renin-angiotensin system inhibitors in oxidative stress-induced endothelial cell dysfunction and H2O2-induced AKT activation remains unclear.Material and methodsHuman coronary artery endothelial cells (HCAECs) were used. The cells were treated with H2O2, captopril, the AKT inhibitor MK-2206, and the AKT activator SC79, either separately, or in combination. p53 and ICAM-1 expression, and p-eNOS, p-Akt and mTOR activation were measured by Western blot. Cell viability was assessed by MTT assay. Levels of reactive oxygen species (ROS) were assayed by flow cytometry. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by wound healing and Transwell assays, respectively.ResultsThe renin-angiotensin system inhibitor captopril reversed H2O2-induced oxidative stress and apoptosis in HCAECs. Co-treatment with captopril and the AKT inhibitor MK-2206 reduced the H2O2-induced P53 and ICAM-1 protein expression (p < 0.05). The proliferation, migration and invasion of HCAECs were significantly enhanced by co-treatment with captopril and MK-2206 (p < 0.05).ConclusionsThe study revealed the protective effect of captopril against H2O2-induced endothelial cell dysfunction through the AKT/mTOR pathway, and its enhancement of cell survival. These findings provide new insights into the protective effects of captopril and novel therapeutic approaches to treatment of cardiovascular disease.

Role of renin-angiotensin system inhibitors in attenuation of dexamethasone-induced ECM remodeling in human trabecular meshwork cells

Background: Trabecular meshwork remodeling leads to aqueous humor outflow resistance and increases intraocular pressure, one of the major risk factor of glaucoma. Renin angiotensin system (RAS) inhibitors are known to attenuate tissue remodeling in cardiovascular system, however their effects on human trabecular meshwork (HTM) are poorly understood.

Role of Renin-Angiotensin System Inhibitors in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

Patients treated with quinapril had a 77% reduction in ischemic events (death, revasculariza-tion, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack stroke; 15% vs 4%; P=0.04). Quinapril was well tolerated and was not asso-ciated with any untoward perioperative hemodynamic events. In a propensity-score-based analysis of 481 patients under-going isolated on-pump CABG,