Hypothalamic GABA and sympathetic regulation in spontaneously hypertensive rats.
The posterior hypothalamus contains a sympathoexcitatory system that can be modulated by changes in GABAergic tone. We tested the hypothesis that the GABAergic mechanism in the posterior hypothalamus is altered in spontaneously hypertensive rats (SHR) compared with the Wistar-Kyoto (WKY) control rats. Blood pressure and heart rate were continuously measured in the conscious state; blood samples were obtained for determination of plasma catecholamine concentrations. Bilateral microinjections of the GABAA receptor antagonist bicuculline methiodide into the posterior hypothalamus increased heart rate and blood pressure in a dose-related fashion and increased plasma catecholamine concentrations in both SHR and WKY rats. The responses were not significantly different between the two strains of rats. Microinjections of the GABAA receptor agonist muscimol in this same region caused dose-related decreases in both heart rate and blood pressure in SHR and WKY rats. Although the decreases in heart rate caused by muscimol were not significantly different between the SHR and WKY rats, the decreases in blood pressure were significantly greater in SHR compared with WKY rats. Further, microinjection of muscimol caused a significant decrease in plasma catecholamines in SHR but not in WKY rats. These data indicate that in SHR and WKY rats the posterior hypothalamus contains a sympathoexcitatory mechanism that is tonically inhibited by GABA. The ability of muscimol to decrease plasma catecholamines selectively in SHR and to cause greater decreases in blood pressure, suggests that the GABAergic mechanisms in the posterior hypothalamus of the SHR and WKY rats may differ.
Wible
J H
JH
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46202-5120.
DiMicco
J A
JA
Luft
F C
FC
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D002395:Catecholamines; D009118:Muscimol; C017069:bicuculline methiodide; D001640:Bicuculline