Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition

Gómez-Roso, Miriam; Montero, María J.; Carrón, Rosalı́a; Sevilla, María A.

doi:10.1111/jphp.12641

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…However, treatment with ZOFE, alone or in combination with an ACE2 inhibitor, led to a beneficial increase in LV fractional shortening and ejection fraction as well as to improvement in diastolic function. ZOFE, due to its high lipophilicity, could potentially easily penetrate cardiac tissue and exert its antiremodeling effect regarding attenuation of LV hypertrophy, fibrosis, and LV functional improvement in SHR [ 27 , 42 , 43 ]. ZOFE was also reported to stimulate active Ca 2+ uptake via the sarcoplasmic reticulum cycle in cardiomyocytes, which could account for the improvement in myocardial contractility after ischemia-reperfusion damage [ 44 ] and improvement of diastolic relaxation in our experiment.…”

Section: Discussionmentioning

confidence: 99%

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

Cacanyiova,

Cebova,

Simko

et al. 2023

Biol Res

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Background Angiotensin 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). Results Zofenopril 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. Conclusions Zofenopril 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.

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Section: Discussionmentioning

confidence: 99%

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

Cacanyiova,

Cebova,

Simko

et al. 2023

Biol Res

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Lycopene-supplemented diet ameliorates cardiovascular remodeling and oxidative stress in rats with hypertension induced by Angiotensin II

Ferreira-Santos

Aparicio

Carrón

et al. 2018

Journal of Functional Foods

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Zofenopril exerts a cardiovascular protective effect on rats infused with angiotensin II beyond angiotensin-converting enzyme inhibition

Abstract: Zofenopril could exert additional beneficial effects beyond ACE inhibition that would justify the improvement of pathophysiological processes triggered by angiotensin II.

Cited by 2 publications

References 23 publications

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

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

Lycopene-supplemented diet ameliorates cardiovascular remodeling and oxidative stress in rats with hypertension induced by Angiotensin II

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