Chronic effects of central and systemic administration of losartan on blood pressure and baroreceptor reflex in spontaneously hypertensive rats.
To clarify the role of endogenous angiotensin II (AngII) in the hypertension of spontaneously hypertensive rats (SHR), we examined the chronic effects of central and systemic administration of losartan, an angiotensin AT1 receptor antagonist, on blood pressure and arterial baroreceptor reflex. The SHR and Wistar-Kyoto rats (WKY), aged 12 to 16 weeks, received subcutaneous infusions of losartan at a dose of 10 mg/kg/day, or intracerebroventricular infusions of losartan at doses of 1 or 10 mg/kg/day for 14 days. Control groups received either isotonic saline solution subcutaneously or intracerebroventricular artificial cerebrospinal fluid. On day 14, baroreflex control of heart rate was determined by intravenous phenylephrine, and pressor response to intravenous AngII (100 ng/kg) was investigated in conscious rats. Blood pressure was higher and the sensitivity of the baroreflex control of heart rate was lower in vehicle-treated SHR than in WKY. Chronic subcutaneous administration of losartan lowered the blood pressure throughout the infusion period in both SHR and WKY, but the hypotensive effects were significantly greater in SHR. Losartan also sensitized the impaired baroreflex in SHR. Chronic intracerebroventricular losartan at a dose of 1 mg/kg/day did not alter the blood pressure or the baroreflex control of the heart rate in either strain. The effects of 10 mg/kg/day of intracerebroventricular losartan on blood pressure and the baroreflex were similar to those of the same dose administered subcutaneously. The pressor response to intravenous AngII was similarly inhibited by intracerebroventricular and subcutaneous losartan doses of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawano
Y
Y
Division of Hypertension and Nephrology, National Cardiovascular Center, Osaka, Japan.
Yoshida
K
K
Matsuoka
H
H
Omae
T
T
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D019808:Losartan; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012018:Reflex / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan