scholarly journals Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: comparison with an angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor

2013 ◽  
Vol 124 (8) ◽  
pp. 529-545 ◽  
Author(s):  
Candice M. Thomas ◽  
Qian Chen Yong ◽  
Rachid Seqqat ◽  
Niketa Chandel ◽  
David L. Feldman ◽  
...  

Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme inhibitors). In the present study, we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin). Diabetic mice were treated with insulin, aliskiren (a renin inhibitor), benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps. Significant impairment in diastolic and systolic cardiac functions was observed in diabetic mice, which was completely prevented by all three RAS (renin–angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes increased cardiac PRR (prorenin receptor) expression and nuclear translocation of PLZF (promyelocytic zinc finger protein), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by PRR represented a novel mechanism in diabetic cardiomyopathy. Differential effects of the three agents on oxidative stress, cytokines and PRR expression suggested subtle differences in their mechanisms of action.

2015 ◽  
Vol 128 (10) ◽  
pp. 649-663 ◽  
Author(s):  
Yixuan Shi ◽  
Chao-Sheng Lo ◽  
Ranjit Padda ◽  
Shaaban Abdo ◽  
Isabelle Chenier ◽  
...  

In summary, our data indicate an important role of Ang-(1–7) in inhibiting intrarenal oxidative stress and subsequent prevention of the development of hypertension and renal injury in diabetic mice.


2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Andrea Laurentius ◽  
Brian Mendel ◽  
Radityo Prakoso

Abstract Background Novel coronavirus disease 2019 has been stated as global disease pandemic due to its rapid spread worldwide. Up to 30% of coronavirus disease 2019 patients with hypertension are more susceptible to death. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been used as primary line of medication for hypertension; nonetheless, conflicting data arises as numerous studies showed contradictory results. Main body Aiming to show clinical outcome of renin-angiotensin-aldosterone system blockers in hospital treatment of hypertensive patients with coronavirus disease 2019, systematically searched literatures through five databases were intensively appraised using The Grading of Recommendations Assessment, Development and Evaluation checklists for cohort studies. Based on the result evaluation from retrospective cohorts involving more than 15,000 patients across Asia and other regions of the world, ten encompassed studies divided into two subgroups in this meta-review showed that in-hospital hypertensive coronavirus disease 2019 patients receiving antihypertensive drugs were associated with overall risk reduction in subgroup 1 (hazard ratio, HR = 0.96, 95% CI = 0.82–1.12) to no outcome association of all-cause mortalities in subgroup 2 (HR = 0.26, 95% CI = 0.19–0.34). All appraised studies in synergism showed that mortality outcomes were not augmented with the employment of either ACE inhibitor or ARB in subjects. Conclusion Therefore, the results support recommendation by the American Heart Association not to discontinue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker regimens in coronavirus disease 2019 patients with hypertension.


2015 ◽  
Vol 28 (3) ◽  
pp. 283 ◽  
Author(s):  
Luís Nogueira-Silva ◽  
João A. Fonseca

Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are first line drugs in the treatment of hypertension. The aim of this review was to assess if there are differences between these drug classes regarding the prevention of total mortality, occurrence of cardiovascular events and of adverse effects. A systematic review and metanalysis was performed, searching for studies that compare angiotensin converting enzyme inhibitors and angiotensin receptor blockers face-to-face, in several databases until July 2014. The study selection and data extraction were performed by 2 independent researchers. Nine studies were included, with a total of 10 963 participants, 9 398 of which participated in the same study and had high cardiovascular risk. No differences were observed regarding total mortality, cardiovascular mortality or total cardiovascular events. A slightly smaller risk was observed with angiotensin receptor blockers regarding withdrawal due to adverse effects (55 people were needed to be treated with angiotensin receptor blockers for 4.1 years to avoid one withdrawal due to adverse effect), mainly due to the occurrence of dry cough with angiotensin converting enzyme inhibitors. Thus, no differences were observed between angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the prevention of total mortality and cardiovascular events, and angiotensin receptor blockers were better tolerated. Given the large proportion of participants with a high cardiovascular risk, the generalization of these results to other populations is limited.


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