Gabaergic stimulation inhibits central actions of angiotensin II: pressor responses, drinking and release of vasopressin.
In conscious rats, intracerebroventricular (i.c.v.) treatment with the GABA agonist muscimol (1-100 ng) suppressed the pressor responses to ANG II (100 ng i.c.v.) in a dose-dependent and reversible fashion. Treatment i.c.v. with GABA (1-500 micrograms) produced a similar but shorter inhibition. Inhibition of endogenous GABA degradation with amino-oxyacetic acid (AOAA, 30 mg/kg i.p.) markedly reduced the pressor responses to ANG II (10-1000 ng i.c.v.) with a recovery period of 24 h. This inhibition was reversed by the GABA antagonist bicuculline (1 microgram i.c.v.). Muscimol (100 ng i.c.v.) did not significantly attenuate the pressor responses to i.c.v. histamine (10 micrograms). Pretreatment with muscimol (100 ng i.c.v.) drastically reduced the drinking responses to i.c.v. ANG II (500 ng) and increased the latency to drink. Muscimol also suppressed drinking induced by carbachol (50 ng i.c.v.). Muscimol (10-1000 ng i.c.v.) inhibited the ANG II (100 ng i.c.v.)-induced release of AVP from the pituitary gland with complete suppression of the response at the highest dose. Our results demonstrate that the GABAergic system exerts an inhibitory control on pathways mediating the various central actions of ANG II, which appears to be most specific for the ANG II-induced pressor responses.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D014667:Vasopressins; D000804:Angiotensin II; D000625:Aminooxyacetic Acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid