The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760

Biological Research

Research Article

Anna Zemancikova¹  Basak G. Aydemir¹  Martina Cebova¹  Iveta Bernatova¹  Andrej Barta¹  Sona Cacanyiova¹  Andrea Berenyiova¹  Michal Kluknavsky¹  Ezgi Shaman¹  Stefan Zorad²  Katarina Krskova²  Fedor Simko³  Tomas Baka⁴ 

[1] Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia;Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia;Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia;Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia;3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia;Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia;

关键词: Essential Hypertension;    ACE2 inhibitor;    Zofenopril, SARS-CoV-2;    Cardiac function;    Vasoactivity;    Hydrogen sulfide;    Nitric oxide;    Mas receptor;   

DOI  :  10.1186/s40659-023-00466-x

 received in 2023-04-18, accepted in 2023-10-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAngiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN).ResultsZofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect.ConclusionsZofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.

【 授权许可】

CC BY   
© Sociedad de Biologia de Chile 2023

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