Effects of centrally administered losartan on deoxycorticosterone-salt hypertension rats

To investigate whether brain AT1 receptor stimulation contributes as a hype rtensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension, losartan (1 mg/4 muL) or artificial cerebrospinal fluid (aCSF) was injecte d into the lateral cerebral ventricle in conscious control uninephrectomize d Wistar rats or rats with DOCA-salt for 2 or 4 weeks, and mean arterial pr essure (MAP) and heart rates (HR) were recorded. In rats with DOCA-salt tre atment, resting MAP increased to 144 +/- 6 mmHg after 2 weeks and to 170 +/ - 5 mmHg after 4 weeks versus 115-120 mmHg in controls. In rats with 2 week DOCA-salt treatment, MAP started declining at 4 hr after intracerebroventr icular (icv) injection of losartan, and significant decreases in MAP were f ound at 18 and 24 hr. In rats with 4 week ll salt treatment, MAP was signif icantly decreased at 4, 18 and 24 hr. In both groups MAP decreased to that of control rats. In control rats, icv losartan had no effect on MAP and HR. Icv aCSF did not significantly change MAP and HR in either DOCA-salt hyper tensive rats or control rats. Normalization of MAP after icv administration of the AT1 receptor antagonist suggests a significant role for brain AT, r eceptor stimulation in the development and maintenance of hypertension in t he DOCA-salt hypertensive rat model.