Roles of peripheral and central angiotensin-converting enzyme (ACE) in hypovolemic thirst induced by compound 48/80 in rats.
Subcutaneous (s.c.) injection of Hoe 498, an angiotensin converting enzyme (ACE) inhibitor, at the doses of 0.1, 0.5, 1.0 and 4.0 mg/kg produced a dose-related inhibition of compound 48/80-induced hypovolemic thirst in rats. A significant time-response relationship was observed between the pretreatment time of Hoe 498 at a dose of 4.0 mg/kg and the inhibition of compound 48/80-induced water intake. Nearly 90% of plasma ACE activity was inhibited by Hoe 498 at all doses used, and this inhibition at the dose of 4.0 mg/kg of Hoe 498 continued for more than 4 hr. Intracerebroventricular (i.c.v.) or s.c. injection of Hoe 498 in doses ranging from 0.5 to 20 micrograms comparably inhibited plasma ACE activity in a dose-dependent manner. The compound 48/80-induced water intake was significantly reduced by i.c.v. injection of Hoe 498 (20 micrograms) 30 min after compound 48/80 administration, but not reduced when the drug was given 15 min prior to injection of dipsogen. The inhibition of water intake by Hoe 498 seems to be dependent on the dose and time between administration of Hoe 498 and compound 48/80. The present data suggest that brain ACE is more involved in compound 48/80-induced water intake than peripheral systemic ACE.
Izumi
H
H
Department of Physiology, Tohoku University School of Dentistry, Miyagi, Japan.
Hayashi
S
S
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013894:Thirst / Q000187:drug effects / Q000502:physiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D000804:Angiotensin II; D003189:p-Methoxy-N-methylphenethylamine; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril