Maternal separation enhances Ang II‐induced constriction by reducing nitric oxide (NO) buffering

Abstract

Previously we reported exacerbated AngII-induced responses, in vitro and in vivo, in adult rats subjected to maternal separation (MS). Acute pre-incubation of aortic rings with a NOS inhibitor (L-NAME) revealed reduced NO buffering in MS rats. We hypothesized that chronic in vivo L-NAME treatment is less effective in increasing blood pressure and aortic AngII-induced constriction in MS rats. MS (n=3) was performed in male WKY rats 3 hs/day from day 2 to 14 of life. Control (n=3) rats were non-MS counterparts. L-NAME was administered in the drinking water from week 14 to 17 of life (10 or 100 mg/Kg/day) with mean arterial pressure (MAP) monitoring. MAP in baseline was similar in control and MS rats (105±1 vs. 103±2 mmHg). MAP increased similarly in control and MS rats (14±4 and 15±1 mmHg) at 10mg/kg/day L-NAME. However, after 3 days on 100mg/kg/day, the change in MAP was significantly less in MS (34±3 mmHg) rats than control (43±1 mmHg, p<0.05). AngII-induced constriction (10−12 to 10−4.5 mol/L) was performed in aortic rings from chronic L-NAME treated rats. Aortas from MS rats displayed reduced AngII-induced constriction compared to control (55±14 vs. 116±13 %max KCl, p<0.05). These data indicate that endogenous NO buffering is reduced in MS rats, which may lead to exaggerated AngII-mediated responses.