Direct Renin Inhibition Prevents Cardiac Dysfunction in a Diabetic Mouse Model: Comparison With an Angiotensin Receptor Antagonist and Angiotensin-Converting Enzyme Inhibitor.
- Authors
- Seqqat, Rachid
- Format
- Article
- Status
- publishedVersion
- Description
Hyperglycemia upregulates intracellular angiotensin II production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than angiotensin receptor blockers (ARBs) or ACE inhibitors. Here we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACE inhibitor. Diabetes was induced in adult mice for 10 wks by streptozotocin. Diabetic mice were treated with insulin, aliskiren (renin inhibitor), benazeprilat (ACE inhibitor), or valsartan (ARB) via subcutaneous minipumps. Significant impairment in diastolic and systolic cardiac function was observed in diabetic mice, which was completely prevented by all three RAS inhibitors. Hyperglycemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, while valsartan was partially effective. Diabetes increased cardiac (pro)renin receptor (PRR) expression and nuclear translocation of promyelocytic zinc finger protein (PLZF), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function as ARBs and ACE inhibitors. 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 mechanism of action.
Universidad de las Fuerzas Armadas-ESPE
https://www.scopus.com/record/display.uri?eid=2-s2.0-84872423393&origin=resultslist&sort=plf-f&src=s&st1=
- Publication Year
- 2013
- Language
- eng
- Topic
- INHIBITION
CARDIAC
DYSFUNCTION
DIABETIC
ENZYME
INHIBITOR
- Repository
- Repositorio SENESCYT
- Rights
- openAccess
- License
- openAccess