Effect of the structural modification of Candesartan with Zinc on hypertension and left ventricular hypertrophy.
Eur J Pharmacol
; 946: 175654, 2023 May 05.
Article
en En
| MEDLINE
| ID: mdl-36930883
ABSTRACT
Hypertension is the most common cause of left ventricular hypertrophy, contributing to heart failure progression. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. Structural modifications were previously performed by our group using Zinc (ZnCand) as a strategy for improving its pharmacological properties. The measurements showed that ZnCand exerts a stronger interaction with the angiotensin II receptor, type 1 (AT1 receptor), reducing oxidative stress and intracellular calcium flux, a mechanism implied in cell contraction. These results were accompanied by the reduction of the contractile capacity of mesangial cells. In vivo experiments showed that the complex causes a significant decrease in systolic blood pressure after 8 weeks of treatment in spontaneously hypertensive rats (SHR). The reduction of heart hypertrophy was evidenced by echocardiography, the histologic cross-sectional area of cardiomyocytes, collagen content, the B-type natriuretic peptide (BNP) marker and connective tissue growth factor (CTGF) and the matrix metalloproteinase 2 (MMP-2) expression. Besides, the complex restored the redox status. In this study, we demonstrated that the complexation with Zn(II) improves the antihypertensive and cardiac effects of the parental drug.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Zinc
/
Hipertrofia Ventricular Izquierda
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Hipertensión
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Antihipertensivos
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Argentina