Resolution of central sites involved in picrotoxin-induced vagal activation and vasopressin release.
This investigation tested the hypotheses that picrotoxin, a drug which blocks the inhibitory effect of gamma-aminobutyric acid (GABA), would, in spinal cord-transected rats, (1) suppress the cardiac vagus when localized to the forebrain and stimulate the cardiac vagus by acting in the brainstem and (2) stimulate the release of vasopressin into the systemic circulation through separate forebrain and brainstem GABAergic mechanisms. An intra-arterial infusion technique allowed for delivery of picrotoxin selectively to either forebrain or brainstem areas. Administration of picrotoxin via the vertebral artery decreased sinus rate and increased circulating levels of vasopressin. Infusion of picrotoxin into the internal carotid artery caused increases in sinus rate, blood pressure and plasma vasopressin. These data support the hypothesis that GABAergic mechanisms at different levels of the neuraxis exert opposite effects on cardiac vagal activity, and that GABAergic mechanisms in both the brainstem and forebrain inhibit the release of AVP into the systemic circulation.
Wible
J H
JH
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
DiMicco
J A
JA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D003655:Decerebrate State; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*
D010852:Picrotoxin; D011963:Receptors, GABA-A; D014667:Vasopressins