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THE EFFECTS OF CENTRAL ADMINISTRATION OF ANGIOTENSIN II TYPE‐1 RECEPTOR ANTAGONIST, CV‐11974, IN NEPHRECTOMIZED SPONTANEOUSLY HYPERTENSIVE RATS
Author(s) -
Kamitani Atsushi,
Higashimori Koichi,
Kohara Katsuhiko,
Higaki Jitsuo,
Mikami Hiroshi,
Ogihara Toshio
Publication year - 1994
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1994.tb02512.x
Subject(s) - endocrinology , medicine , nephrectomy , renin–angiotensin system , angiotensin ii , blood pressure , antagonist , angiotensin ii receptor antagonist , kidney , receptor , angiotensin receptor
SUMMARY 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.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.