title: Anti-hypertensive Effects of Diminazene Aceturate: An Angiotensin- Converting Enzyme 2 Activator in Rats.
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.
authors.forename: Marilda L A
authors.initials: ML
authors.lastname: De Maria
authors.forename: Liliane D
authors.initials: LD
authors.lastname: Araújo
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Fraga-Silva
authors.forename: Letícia A S
authors.initials: LA
authors.lastname: Pereira
authors.forename: Heder J
authors.initials: HJ
authors.lastname: Ribeiro
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Menezes
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.affiliation: Department of Morphology - Av. Antônio Carlos, 6627 - ICB - UFMG 31.270-901 - Belo Horizonte, MG, Brazil. anderson@icb.ufmg.br.
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ferreira
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C003915:diminazene aceturate; D019331:NG-Nitroarginine Methyl Ester; D004133:Diminazene