Regulation of cardiovascular sympathetic neurons by substance P and gamma-aminobutyric acid in the rat spinal cord.
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.
Hasséssian
H
H
Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.
Prat
A
A
De Champlain
J
J
Couture
R
R
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000294:innervation; D002395:Catecholamines / Q000097:blood; D058787:GABA-A Receptor Antagonists; D005998:Glycine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000502:physiology*
D002395:Catecholamines; D058787:GABA-A Receptor Antagonists; D009478:Neuropeptide Y; D011963:Receptors, GABA-A; C052329:phaclofen; D009118:Muscimol; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D002211:Capsaicin; D005998:Glycine; D001640:Bicuculline