Zinc complexation improves angiotensin II receptor type 1 blockade and in vivo antihypertensive activity of telmisartan
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.
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Martinez, V. R., Aguirre, M. V., Todaro, J. S., Martins Lima, A., Stergiopulos, N., Ferrer, E. G., & Williams, P. (2021). Zinc complexation improves angiotensin II receptor type 1 blockade and in vivo antihypertensive activity of telmisartan. Future Medicinal Chemistry, 13(1), 13–23. https://doi.org/10.4155/fmc-2020-0093
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WOS:000594767500001
2021
13
1
13
23
REVIEWED
EPFL