Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age

Abstract

We investigated the effect of age on cardiovascular responses mediated by central angiotensin II (AngII) after intracerebroventricular infusion of AngII, and during restraint stress. Blood pressure (BP) and heart rate (HR) of young (5-month-old) and old (27-month-old) male Fischer-344 x Brown-Norway rats were measured using radiotelemetry. AngII was infused intracerebroventricularly using osmotic minipumps (10 ng/0.5 microl/h for 11 days). BP and HR responses to stress were evaluated by placing animals in restrainers for 20 min before and after intracerebroventricular infusion of the AngII-type-1 receptor inhibitor losartan (15 microg/microl per h for 3 days). Resting BP was significantly elevated and HR was significantly lower in old rats compared with young. AngII-induced BP increase was markedly reduced in old rats, but HR responses were similar. Diurnal variation of both BP and HR was lower in old animals, and AngII reduced the amplitude of BP variation in young rats, but not in old. Restraint stress-induced BP and HR elevations were reduced with age. BP responses were diminished by central losartan infusion in both young and old, but this effect was more significant in young rats. In addition, expression of CuZn-superoxide dismutase and catalase declined significantly with age in the hypothalamus, whereas baseline oxidative stress increased. In contrast, AngII-induced increase in hypothalamic oxidative stress decreased with age. This study demonstrates that the role of central AngII diminishes with age in the regulation of BP both during baseline conditions and during stress, whereas the involvement of AngII in the regulation of HR remains unaffected.