Effect of inhibition of central angiotensin pressor mechanisms on blood pressure in spontaneously hypertensive rats.
The present experiments were designed to elucidate the role of central angiotensin II (AII) mechanisms in maintenance of established hypertension in adult spontaneously hypertensive rats (SHR) by determining the blood pressure response to chronic intraventricular (i.v.t.) infusion of the converting enzyme inhibitor teprotide or the AII receptor antagonist 1sar,8Thr-AII (sarthran). Male SHR (240-300 g) were given chronic indwelling arterial and venous catheters and bilateral lateral cerebral ventricular cannulae. The acute pressor responses to successive intravenous infusions of AII (sarthran experiments) or angiotensin I (AI; teprotide experiments) and to an intraventricular bolus injection of AII or AI were determined in the conscious rats. A 5-day intraventricular infusion of sarthran (1 or 6 micrograms/h) or teprotide (10 micrograms/h) in isotonic saline was maintained by subcutaneously implanted osmotic minipumps, and pressor responses were retested on the 5th day of intraventricular infusion. Five-day intraventricular sarthran infusion at 1 and 6 micrograms/h reduced the pressor response to intraventricular AII by 48 and 74%, respectively, while intraventricular teprotide (10 micrograms/h) inhibited the pressor response to intraventricular AI by 25%. None of the intraventricular infusions significantly decreased pressor responsiveness to intravenous AII or AI. In separate groups of SHR, tail-cuff blood pressure was monitored before, during, and after a 1-week intraventricular teprotide infusion (10 micrograms/h) or successive intraventricular infusions of sarthran at 1 microgram/h for 2 weeks followed by 6 micrograms/h for 1 week. Neither chronic intraventricular sarthran or teprotide caused a significant lowering of blood pressure in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D007276:Injections, Intraventricular; D051381:Rats; D011918:Rats, Inbred SHR; D013722:Teprotide / Q000494:pharmacology
D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D013722:Teprotide