Stimulation of vasopressin release by gamma-aminobutyric acid antagonists in spinal cord transected rats.
Picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, administered to spinal rats elicited dose-related increases in mean blood pressure and circulating plasma vasopressin concentration which were found to be highly correlated (r = 0.952; P less than .001) 6 min after infusion of picrotoxin. Pretreatment with the vasopressin antagonist d(CH2)5Tyr(Me)arginine vasopressin (10 microgram/kg i.v.) blocked the picrotoxin-induced pressor response. Administration of bicuculline (1.0 mg/kg i.v.), a second GABA antagonist, caused an increase in mean blood pressure and plasma vasopressin, whereas strychnine, another central nervous system stimulant thought not to act via a GABAergic mechanism, failed to evoke a significant change in either mean blood pressure or plasma vasopressin. Midcollicular decerebration decreased base-line plasma vasopressin concentrations and also prevented the picrotoxin-induced increase in pressure and vasopressin. The data from this study suggest that blockade of tonic GABAergic inhibition by GABA antagonists causes the release of vasopressin into the systemic circulation which results in a pressor response in spinal rats. The level at which this GABAergic inhibition occurs is not known; however, the GABA antagonists appear to require an intact supraspinal neuraxis to cause the release of vasopressin from the neurohypophysis.
Wible
J H
JH
Zerbe
R L
RL
DiMicco
J A
JA
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D018756:GABA Antagonists; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*
D001127:Arginine Vasopressin; D001640:Bicuculline; D018756:GABA Antagonists; D010852:Picrotoxin; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A