Dutra, Joao B. R.Lacerda, Ismaley S.Nunes, Allancer D. C.Bessa, Amanda S. M.Jesus, Erika F.Pontes, Carolina N. R.Naves, Lara M.Pedrino, Gustavo R.Mendes, Elizabeth P.Fraga-Silva, Rodrigo A.Costa-Fraga, Fabiana P.Stergiopulos, NikosKangussu, Lucas M.Faraco, Andre A. G.Ferreira, Anderson J.Castro, Carlos H.2022-07-182022-07-182022-07-182022-09-0110.1016/j.lfs.2022.120693https://infoscience.epfl.ch/handle/20.500.14299/189379WOS:000814755000006Aims:Diminazene aceturate, a putative ACE2 activator, is susceptible to cleavage resulting in the formation of paminobenzamidine (PAB). This study aimed to investigate the effects of PAB in addressing cardiovascular dysfunctions in spontaneously hypertensive rats (SHR). Main methods:Acute effects of PAB on mean arterial pressure (MAP), heart rate (HR), and aortic (AVC) and mesenteric vascular conductance (MVC) were evaluated in anesthetized SHR. Isolated aortic rings and the Langendorff technique were used to investigate the acute and chronic effects of PAB in the artery and heart. Chronic treatment with PAB (1 mg/kg, gavage) was carried out for 60 days. During this period, systolic blood pressure (SBP) and HR were measured by tail-cuff plethysmography. After the treatment, the left ventricle was collected for histology analyses, western blotting, and ACE2 activity. Key findings:Bolus infusion of PAB acutely reduced MAP and increased both AVC and MVC in SHR. Additionally, PAB induced coronary and aorta vasodilation in isolated organs from Wistar and SHR in an endothelialdependent manner. The chronic PAB treatment in SHR significantly attenuated the increase of SBP and improved the aorta vasorelaxation induced by acetylcholine and bradykinin-induced coronary vasodilation. In addition, chronic treatment with PAB attenuated the cardiomyocyte hypertrophy and extracellular matrix deposition in hearts from SHR. PAB did not alter the protein expression of the AT1, AT2, Mas, ACE, ACE2, or ACE2 activity. Significance:PAB induced beneficial effects on cardiovascular dysfunctions induced by hypertension, suggesting that this molecule could be used in the development of new drugs for the treatment of cardiovascular diseases.Medicine, Research & ExperimentalPharmacology & PharmacyResearch & Experimental Medicineserine proteasecardiovascular dysfunctionshypertensive ratsace2angiotensin-converting enzymediminazene aceturatecardiac-hypertrophyrenin-angiotensinserine proteasesblood-pressureidentificationactivationpreventionfibrosistext::journal::journal article::research article