Injection of ramipril into the lateral ventricle interferes with the drinking response induced by pharmacological and natural thirst stimuli.
We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (i.c.v.) injection of ramipril (1 microgram/microliter) significantly reduced drinking in response to subcutaneous (s.c.) injection of isoprenaline (100 micrograms/kg) from 8.49 +/- 0.69 to 2.96 +/- 0.36 ml/2 h, polyethyleneglycol (PEG) (30% w/v, 10 ml/kg) from 9.51 +/- 2.20 to 1.6 +/- 0.34 ml/2 h or water deprivation for 24 h from 12.61 +/- 0.83 to 5.10 +/- 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCI). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested.
Saad
W A
WA
Departamento de Ciências Fisiológicas, Faculdade de Odontologia, Universidade Estadual Paulista, Araraquara, Brasil.
Luiz
A C
AC
Camargo
L A
LA
Menani
J V
JV
Renzi
A
A
Silveira
J E
JE
Paulino
M A
MA
Saad
W A
WA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014868:Water Deprivation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril