GABAB receptor-mediated inhibition of the neurogenic vasopressor response in the pithed rat.
1. The effects of gamma-aminobutyric acid (GABA) and related drugs on the vasopressor response induced by electrical stimulation (single pulse of 30 V and 1 ms) of the preganglionic sympathetic nerve fibres or by injection of noradrenaline 0.3 nmol kg-1 were studied in the pithed rat. 2. The electrically-induced increase in diastolic blood pressure was inhibited by GABA and the GABAB-receptor agonist R-(--)-baclofen but was not affected by its S-(+)-enantiomer and by the GABAA-receptor agonists muscimol and 3-aminopropane sulphonic acid. 3. The dose-response curve of R-(--)-baclofen for its inhibitory effect on the electrically-induced vasopressor response was shifted to the right by the GABAB-receptor antagonist 2-hydroxysaclofen, but was not affected by the GABAA-receptor antagonist bicuculline. 2-Hydroxysaclofen and bicuculline by themselves did not affect the electrically-induced vasopressor response. 4. The increase in diastolic blood pressure induced by exogenous noradrenaline was not affected by the GABA-related drugs, which also had no (or very slight) effects on the basal diastolic blood pressure. 5. It is concluded that GABA inhibits catecholamine release in the resistance vessels of the rat via GABAB-receptors, probably located presynaptically on the postganglionic sympathetic nerve fibres.
Kohlenbach
A
A
Institute of Pharmacology and Toxicology, University of Bonn, Fed. Rep. Germany.
Schlicker
E
E
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004558:Electric Stimulation; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D013654:Taurine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate; D001418:Baclofen; D014403:Tubocurarine; D009638:Norepinephrine; C057491:2-hydroxysaclofen; D001640:Bicuculline