Article date: 1991/9/4
PubMed ID: 1723952
Journal name: European journal of pharmacology (ISSN: 0014-2999)
The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.
Author List: Hasséssian H, Prat A, De Champlain J, Couture R
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Catecholamines; GABA-A Receptor Antagonists; Neuropeptide Y; Receptors, GABA-A; phaclofen; Muscimol; Substance P; gamma-Aminobutyric Acid; Baclofen; Capsaicin; Glycine; Bicuculline;
Mesh terms: Animals; Baclofen/analogs & derivatives; Bicuculline/pharmacology; Blood Pressure/drug effects; Capsaicin/pharmacology; Cardiovascular Physiological Phenomena; Cardiovascular System/innervation; Catecholamines/blood; GABA-A Receptor Antagonists; Glycine/pharmacology; Heart Rate/drug effects; Injections, Spinal; Male; Muscimol/pharmacology; Neurons/drug effects; Neuropeptide Y/blood; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Spinal Cord/drug effects; Substance P/pharmacology; Sympathetic Nervous System/drug effects; gamma-Aminobutyric Acid/analogs & derivatives;