2. Academic Validation
  3. p-Aminobenzamidine attenuates cardiovascular dysfunctions in spontaneously hypertensive rats

p-Aminobenzamidine attenuates cardiovascular dysfunctions in spontaneously hypertensive rats

  • Life Sci. 2022 Sep 1:304:120693. doi: 10.1016/j.lfs.2022.120693.
João B R Dutra 1,  Ismaley S Lacerda 1,  Allancer D C Nunes 2,  Amanda S M Bessa 1,  Érika F Jesus 1,  Carolina N R Pontes 1,  Lara M Naves 1,  Gustavo R Pedrino 1,  Elizabeth P Mendes 1,  Rodrigo A Fraga-Silva 3,  Fabiana P Costa-Fraga 3,  Nikos Stergiopulos 3,  Lucas M Kangussu 4,  André A G Faraco 5,  Anderson J Ferreira 6,  Carlos H Castro 7
Affiliations

Affiliations

  • 1 Department of Physiological Sciences, Federal University of Goiás, Goiânia, GO 74690-900, Brazil.
  • 2 Department of Physiological Sciences, Federal University of Goiás, Goiânia, GO 74690-900, Brazil; Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis 55455, MN, USA.
  • 3 Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • 4 Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
  • 5 Department of Pharmaceutical Products, Federal University of Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
  • 6 Medical School, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, MG, Brazil.
  • 7 Department of Physiological Sciences, Federal University of Goiás, Goiânia, GO 74690-900, Brazil. Electronic address: castro@ufg.br.
PMID: 35688180 DOI: 10.1016/j.lfs.2022.120693
Abstract

Aims: 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).

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 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.

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.

Keywords

ACE2; Cardiovascular dysfunctions; Hypertensive rats; Serine protease.

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