Submit Manuscript  

Article Details


Anti-hypertensive Effects of Diminazene Aceturate: An Angiotensin- Converting Enzyme 2 Activator in Rats

[ Vol. 23 , Issue. 1 ]

Author(s):

Marilda L.A. De Maria, Liliane D. Araújo, Rodrigo A. Fraga-Silva, Letícia A.S. Pereira, Heder J. Ribeiro, Gustavo B. Menezes, Vinayak Shenoy, Mohan K. Raizada and Anderson J. Ferreira   Pages 9 - 16 ( 8 )

Abstract:


Previous studies have shown that activation of endogenous angiotensin-converting enzyme 2 (ACE2) results in various beneficial effects in the cardiovascular system. Recently, a new ACE2 activator, named diminazene aceturate (DIZE), was described. Here, we evaluated the actions of this compound in blood pressure (BP) and heart rate (HR) of conscious normotensive and hypertensive rats, as well as explored its mechanism of actions using isolated vessels. The renovascular model of hypertension was utilized. The participation of the Angiotensin-(1-7) receptor Mas and nitric oxide (NO) in the effects of DIZE was evaluated using A-779 and L-NAME, respectively. It was observed that DIZE caused a marked decrease in BP with a compensatory increase in HR in nornotensive rats. Accordingly, a significant reduction in the blood flow of the mesenteric bed was evidenced using intravital microscopy. Moreover, in rats with renovascular hypertension, DIZE caused a decrease in BP similar to the hypotensive effect induced by captopril. Importantly, this compound also prevented the development of cardiac hypertrophy induced by hypertension. The isolated vessels technique revealed that the vasodilator effects of DIZE were dependent on Mas activation and NO release. Thus, our findings demonstrated that DIZE reduces the BP of normotensinve and hypertensive rats possibly by a mechanism involving Mas and NO.

Keywords:

Angiotensin-(1-7), angiotensin-converting enzyme 2, aortic vessels, Mas receptor, renin-angiotensin system, renovascular hypertension, intravital microscopy.

Affiliation:

Department of Morphology - Av. Antônio Carlos, 6627 - ICB - UFMG 31.270-901 - Belo Horizonte, MG, Brazil

Graphical Abstract:



Read Full-Text article