Cerebroventricular injection of angiotensin II antagonist: effects on blood pressure responses to central and systemic angiotensin II.
Circulating angiotensin II (ANG II) has several physiological effects that result from interaction of the peptide with AT1 receptors in the brain. Our purpose was to determine if selective pharmacological blockade of brain AT1 receptors would reverse chronic low-dose ANG II-induced hypertension. Male Sprague-Dawley rats were instrumented with chronic indwelling arterial and venous catheters and a lateral intracerebroventricular (i.c.v.) cannula. All rats received ANG II i.v. for 15 days at a dose of 4 ng.min-1. On days 2, 7 and 12 of the ANG II infusion a bolus of an AT1 receptor antagonist, the active metabolite of losartan, EXP 3174 (1 microgram in 2 microliters of saline, i.c.v.; n = 5) or vehicle (2 microliters of saline; n = 2) was administered into the cerebrospinal fluid. Mean arterial pressure and heart rate were measured at numerous time points after this injection. Although the dose of EXP 3174 used in preliminary experiments was shown to block the responses to i.c.v. ANG II this treatment did not lower MAP in chronic ANG II-hypertension. These results suggested that either ANG II-hypertension does not involve brain AT1 receptors, or that i.c.v. EXP 3174 may not gain access to brain sites at which circulating ANG II acts to produce hypertension. To test this latter possibility ANG II was microinjected into the area postrema of anesthetized rats. The area postrema is one of several circumventricular organs at which circulating ANG II may act to influence arterial pressure regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Gorbea-Oppliger
V J
VJ
Michigan State University, Department of Pharmacology and Toxicology, East Lansing, USA.
Fink
G D
GD
D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066026:losartan carboxylic acid; D019808:Losartan