The effects of central administration of angiotensin II type-1 receptor antagonist, CV-11974, in nephrectomized spontaneously hypertensive rats.
1. The role of the brain renin-angiotensin system in the pathogenesis of genetic hypertension was evaluated using a specific non-peptide angiotensin II type-1 receptor antagonist, TCV-116. 2. CV-11974 (active metabolite of TCV-116) was acutely injected either intravenously (i.v.) or intracerebroventricularly (i.c.v) in male spontaneously hypertensive rats (SHR; 12 week old). In separate groups of nephrectomized and sham-operated SHR, graded doses of CV-11974 were administered either i.v. or i.c.v. for 2 days using an osmotic minipump. In another group, the effects of nephrectomy on the depressor effect of chronic treatment with CV-11974 were investigated. Haemodynamics at three points: before infusion, before nephrectomy and 48 h after nephrectomy, were monitored. 3. Acute i.c.v. injection of CV-11974 decreased blood pressure in the presence of the kidney. Prolonged i.c.v. administration of the drug for 2 days decreased blood pressure even at the lowest dosage, which had no hypotensive effects when given i.v. The hypotensive effect of centrally administered CV-11974 was noted even 48 h after bilateral nephrectomy. 4. These results suggest that the brain renin-angiotensin system has a primary role in the maintenance of hypertension after eliminating the circulating renin-angiotensin system in SHR.
Kamitani
A
A
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Higashimori
K
K
Kohara
K
K
Higaki
J
J
Mikami
H
H
Ogihara
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C081643:candesartan