Peripheral administration of AT1 receptor blockers and pressor responses to central angiotensin II and sodium.
Central administration of AT1 receptor blockers prevents salt-sensitive hypertension and inhibits progression of CHF. We investigated in Wistar rats the effectiveness of peripheral administration of two AT1 receptor blockers, losartan and embusartan, in exerting central AT1 receptor blockade. Losartan or embusartan at doses of 30 and 100 mg/kg were administered subcutaneously (s.c.) as a single dose, or one dose daily for 6 days. The BP responses to intracerebroventricular (i.c.v.) injection of Ang II, i.c.v. infusion of Na+-rich aCSF (0.3 M NaCl), and intravenous (i.v.) injection of Ang II were then measured. Losartan or embusartan at 30 and 100 mg/kg both inhibited the BP increases induced by i.c.v. Ang II and, to a lesser extent, by Na+-rich aCSF. After a single dose, this inhibition was more pronounced for losartan. However, after 6 days of treatment, there were no significant differences between the effects of losartan and embusartan. Losartan and embusartan blocked responses to Ang II i.v. 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 AT1 receptor blockers are similarly effective in inhibiting AT1 receptors in the central nervous system, when assessed by pressor responses to acute increases in CSF Na+ or CSF Ang II.
Zhang
J
J
Hypertension Unit, University of Ottawa Heart Institute, ON, Canada.
Leenen
F H
FH
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D017933:Peripheral Nervous System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D012964:Sodium / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D004095:Dihydropyridines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; C109119:embusartan; D012964:Sodium; D019808:Losartan