p-Aminobenzamidine attenuates cardiovascular dysfunctions in spontaneously hypertensive rats

• Published in: Life sciences (1973) 2022-09, Vol.304, p.120693-120693, Article 120693
• Main Authors: Dutra, João B.R., Lacerda, Ismaley S., Nunes, Allancer D.C., Bessa, Amanda S.M., Jesus, Érika F., Pontes, Carolina N.R., Naves, Lara M., Pedrino, Gustavo R., Mendes, Elizabeth P., Fraga-Silva, Rodrigo A., Costa-Fraga, Fabiana P., Stergiopulos, Nikos, Kangussu, Lucas M., Faraco, André A.G., Ferreira, Anderson J., Castro, Carlos H.
• Format: Article
• Language: English
• Subjects: ACE2; Cardiovascular dysfunctions; Hypertensive rats; Serine protease
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120693

Diminazene aceturate, a putative ACE2 activator, is susceptible to cleavage resulting in the formation of p-aminobenzamidine (PAB). This study aimed to investigate the effects of PAB in addressing cardiovascular dysfunctions in spontaneously hypertensive rats (SHR). 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. 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 endothelial-dependent 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. 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.