INTERACTION OF ZINC WITH AN ANGIOTENSIN RECEPTOR ANTAGONIST. IMPROVEMENT OF THE AT1R BLOCKADE AND THE ANTIHYPERTENSIVE ACTIVITY

MARTINEZ, VALERIA ROMINA; MARTINS LIMA, AUGUSTO; STERGIOPULOS, NIKOLAOS; VELEZ RUEDA, OMAR; LOFEUDO, JUAN MANUEL; FERRER, EVELINA GLORIA; DE GIUSTI, VERÓNICA; WILLIAMS, PATRICIA ANA MARÍA

Buenos Aires

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA, SOCIEDAD ARGENTINA DE INMUNOLOGÍA, SOCIEDAD ARGENTINA DE FISIOLOGÍA

Structural modification of drugs is a strategy for improving their pharmacological properties. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. We have previously modified its structure by the addition of Zinc (ZnCand), an essential trace element that contributes to the maintenance of cell redox balance.In this study, we analyze the antihypertensive effects and cellular mechanisms of action of ZnCand in comparison to Cand. For in vivo experiments, SHR male rats were treated with 10-13 mg/ kg/day Cand or ZnCand for 6 weeks and the systolic blood pressure (SBP) was measured. For hypertrophy response, rats were monitored echocardiographically, then hearts (HW) and body (BW) were weighed to calculate HW/BW, LVMI (left ventricular mass index) (LVMI) and LVM/TL (TL: tibial length). For in vitro procedures, transfected HEK293 cells with the angiotensin type 1 receptor (AT1R) were coincubated with 0.1, 1 and 10 μM of Cand or ZnCand and TAMRA-Ang II, for competitive binding assay, or Ang II for ROS andcalcium determinations. ZnCand produced slightly higher SBP reduction (33.5±2.9%, p