Central effects of peripheralley administered AT(1)-receptor blockers.

Abstract

We investigated in Wistar rats (1) the effectiveness of peripheral administration of two AT1-receptor blockers (losartan and embusartan) to cause central AT1-receptor blockade, and (2) whether chronic peripheral treatment with losartan or embursartan can exert sufficient central effects to prevent the central effects of ouabain and sodium. In the first set of experiments, losartan or embursartan at 30 and 100 mg/kg were administered subcutaneously (sc) as a single dose or 1 dose daily for 6 days. The BP responses to intracerebroventricular (icv) injection of Ang II, icv infusion of Na +-rich aCSF (0.3 M NaCl) and intravenous (iv) injection of Ang II were then measured. In the second set of experiments, losartan or embusartan (both at 100mg/kg/day) were given se once daily for 16 days. Ouabain or sodium-rich aCSF were given in these groups of rats by osmotic minipump for 13--14 days. The mean arterial pressure (MAP) at rest and in response to air stress, and icv injection of guanabenz (75 mug/7.5 mul, and 25 mug/2.5 mul), Ang II (30 ng/3 mul) and ouabain (0.5 mug/2 mul) at a 10 minutes interval were then measured. (Abstract shortened by UMI.)