Mechanism of captopril-induced drinking.
Captopril (SQ 14,225), an orally active angiotensin I-converting enzyme (ACE) inhibitor, increased drinking and produced water diuresis in rats when given orally at a dose of 100 mg.kg-1.day-1. Chronic intraperitoneal infusion of angiotensin (ANG) II or the ANG II antagonist [Sar1, Ile8]ANG II abolished this response. Intracerebroventricular (icv) captopril infused chronically reduced the dipsogenic response to oral captopril. [Sar1, Ile8]ANG II (icv) was without effect on captopril-induced drinking. These results suggest that drinking produced by chronic oral treatment of rats with captopril may be caused by the effects of the elevated ANG I concentrations achieved after blockade of ACE and stimulation of renin secretion by captopril. Systemic ANG II may reduce this response by decreasing renin secretion. Systemic [Sar1, Ile8]ANG II presumably blocks brain ANG receptors for blood-borne ANG. Since icv [Sar1, Ile8]ANG II is ineffective, the receptors for systemic and icv ANG appear to be distinct. Orally administered captopril does not diffuse into the brain.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects*; D009994:Osmolar Concentration; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D014556:Urine
D000804:Angiotensin II; D011392:Proline; D002216:Captopril