Beneficial Effects of the Angiotensin-Converting Enzyme 2 Activator Dize in Renovascular Hypertension

Abstract

Background: Angiotensin Converting Enzyme (ACE) 2 is an important modulator of the Renin Angiotensin System (RAS) and the RAS plays a central role in renovascular hypertension. Very few studies investigated the role of components of the counterregulatory RAS axis (ACE2, Ang-(1-7) and Mas receptor) in renovascular hypertension and the results are controversial.

Objective: The aim of this study was to investigate the effects of Diminazene Aceturate (DIZE) administration on renal function and renal inflammation parameters in 2K1C hypertensive rats.

Methods: Male Wistar rats were divided into three experimental groups: sham-operated animals, 2K1C+saline and 2K1C+DIZE orally (1 mg/kg/day). At the end of the 30 days of treatment, renal function was analyzed and kidneys from all the groups were collected and processed separately for measurement of N-acetyl-beta-D-glucosaminidase (NAG) and Myeloperoxidase (MPO) activities, cytokines, chemokines and nitric oxide levels.

Results: Oral DIZE administration for 4 weeks in hypertensive rats attenuated renal dysfunction and reduced the levels of MPO and NAG, cytokines and chemokines (IL1β, IL-6, TNF-α and MCP-1) and increased urinary nitrate/nitrite levels in 2K1C hypertensive rats.

Conclusion: Our findings showed that ACE2 activation may effectively improve renal alterations and inflammation induced by renovascular hypertension.

Keywords: ACE2 activation; angiotensin-(1-7); diminazene aceturate; renin angiotensin system; renoprotection; renovascular hypertension..