INVESTIGADORES
FERRER Evelina Gloria
artículos
Título:
Zinc complexation improves angiotensin II receptor type 1 blockade and in vivo antihypertensive activity of telmisartan
Autor/es:
MARTÍNEZ, VALERIA R.; AGUIRRE, MARIÁ V.; TODARO, JUAN S.; LIMA, AUGUSTO MARTINS; STERGIOPULOS, NIKOLAOS; FERRER, EVELINA G.; WILLIAMS, PATRICIA A.M.
Revista:
Future Medicinal Chemistry
Editorial:
Future Medicine Ltd.
Referencias:
Año: 2021 vol. 13 p. 13 - 23
ISSN:
1756-8919
Resumen:
Background: Angiotensin II receptor blockers were designed as therapeutic agents to block the binding site of the angiotensin II receptor type 1 (AT1R). Methodology: The structure of telmisartan was modified by coordination to the biometal Zn(II), resulting in the compound ZnTelm. Its antihypertensive activity and cellular mechanisms in comparison to telmisartan were studied. Results: Compared with telmisartan, ZnTelm displayed stronger binding to AT1R (binding studies on AT1R-transfected human embryonic kidney cells) and a greater reduction of reactive oxygen species and cytosolic calcium concentration induced by angiotensin II. The antihypertensive activity of the complex (assessed in an N(G)-Nitro-L-arginine methyl ester-induced hypertension model) was significantly higher. ZnTelm also reduced hypertrophy in aortic artery rings and tubular collagen deposition. Conclusion: ZnTelm enhances the AT1R blockade and consequently its antihypertensive effect. Newlands Press.