Hypothalamic GABA suppresses sympathetic outflow to the cardiovascular system.
We studied the cardiovascular effects of altering GABA-ergic tone in the posterior hypothalamus in rats. Animals were equipped with chronic guide cannulas placed in the posterior hypothalamus, arterial and venous catheters, and a bipolar electrode on the splanchnic nerve. Microinjected bilaterally into the posterior hypothalamus in conscious rats, the postsynaptic gamma-aminobutyric acid (GABA) antagonists bicuculline methiodide and picrotoxin rapidly increased heart rate, blood pressure, and sympathetic nerve activity. Microinjection of the GABA agonist muscimol into this same region decreased heart rate, blood pressure, and sympathetic nerve activity in conscious rats. In contrast, muscimol infused into the posterior hypothalamus of anesthetized rats failed to alter heart rate or blood pressure. We conclude that 1) the posterior hypothalamus contains a sympathoexcitatory system that is modulated by changes in GABA-ergic tone and 2) tonic GABA-ergic inhibition is sufficient to completely suppress the activity of this hypothalamic sympathoexcitatory system in anesthetized animals but not in conscious rats.
Wible
J H
JH
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Luft
F C
FC
DiMicco
J A
JA
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D018756:GABA Antagonists; D006339:Heart Rate / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013331:Strychnine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D001640:Bicuculline; D018756:GABA Antagonists; D009118:Muscimol; D009599:Nitroprusside; D010656:Phenylephrine; D010852:Picrotoxin; D013331:Strychnine; C017069:bicuculline methiodide