Enhanced depressor effect of muscimol in the DOCA/NaCl hypertensive rat: evidence for altered GABAergic activity in brain.
To elucidate the role of the central gamma-aminobutyric acid (GABA) system in the maintenance of deoxycorticosterone (DOCA)NaCl hypertension, the responses of mean arterial pressure (MAP), plasma norepinephrine (NE), and epinephrine (EP) to intracerebroventricular (ICV) administration of muscimol, a GABA agonist, and the responses of MAP to bicuculline, a GABA antagonist, and to clonidine, an alpha 2-adrenoceptor agonist known to lower blood pressure by inhibiting sympathetic tone, were examined in conscious, unrestrained 4 week DOCA/NaCl hypertensive rats and age-matched uninephrectomized control rats. Muscimol (50-1000 ng/300 g, ICV) caused dose-dependent decreases in MAP which were greater in DOCA/NaCl rats than in controls. Basal plasma NE and EP were significantly higher in DOCA/NaCl rats than in controls. Muscimol (1000 ng/300 g, ICV) induced decreases in plasma EP which were greater in DOCA/NaCl rats than in controls without changing NE levels in either group. Bicuculline (3 micrograms/300 g, ICV) caused increases in MAP which were the same in both groups. The depressor response to clonidine (5 micrograms/300 g) was greater in DOCA/NaCl rats than in controls. These results suggest that the activity of the central GABAergic system is altered in the rat with established DOCA/NaCl hypertension and that the alteration in central GABAergic function may be related to the increased sympathoadrenal activity and the maintenance of hypertension in this model.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry; D003000:Clonidine / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000633:toxicity; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D018756:GABA Antagonists; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D012965:Sodium Chloride / Q000633:toxicity; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D009118:Muscimol; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D009638:Norepinephrine; D001640:Bicuculline; D004837:Epinephrine