Peripheral administration of AT(1) receptor blockers and pressor responsesto central angiotensin II and sodium

Central administration of AT(1) receptor blockers prevents salt-sensitive h ypertension and inhibits progression of CHF. We investigated in Wistar rats the effectiveness of peripheral administration of two AT(1) receptor block ers, losartan and embusartan, in exerting central AT(1) receptor blockade. Losartan or embusartan at doses of 30 and 100 mg/kg were administered subcu taneously (sc) as a single dose, or one dose daily for 6 days. The BP respo nses to intracerebroventricular (icv) injection of Ang II, icv infusion of Na+-rich aCSF (0.3 M NaC1), and intravenous (iv) injection of Ang II were t hen measured. Losartan or embusartan at 30 and 100 mg/kg both inhibited the BP increases induced by icv Ang II and, to a lesser extent, by Na+-rich aC SF. After a single dose, this inhibition was more pronounced for losartan. However, after 6 days of treatment, there were no significant differences b etween the effects of losartan and embusartan. Losartan and embusartan bloc ked responses to Ang II iv to a similar extent. These results indicate that results from single-dose studies may not reflect the chronic steady-state, and that during chronic treatment both AT(1) receptor blockers are similar ly effective in inhibiting AT(1) receptors in the central nervous system, w hen assessed by pressor responses to acute increases in CSF Na+ or CSF Ang II.