Interaction of Zinc with an angiotensin receptor antagonist. Improvement of the AT1R blockade and the antihypertensive activity.

MARTÍNEZ, VALERIA R.; MARTINS LIMA, A; STERGIOPULOS, NIKOLAOS; VELEZ RUEDA, OMAR; LOUFEDO, JUAN MANUEL ; FERRER, E.G.; DE GIUSTI, VERÓNICA; WILLIAMS, P.A.M.

Buenos Aires-online

Encuentro; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2020; 2020

Fundación Revista Medicina

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 or 13 mg/kg/day Cand or ZnCand respectively, for 8 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 and calcium determinations.ZnCand produced slightly higher SBP reduction (33.5±2.9%, p