Evidence for a GABA(B) receptor component in the spinal action of Substance P (SP) on arterial blood pressure in the awake rat.
1 The activation of tachykinin NK(1) receptors in the rat spinal cord produced a transient drop in arterial blood pressure followed by a more prolonged pressor effect which is mediated by the stimulation of the sympatho-adrenal system. This study aims at characterizing the spinal mechanism of that initial hypotension occurring in awake unrestrained rats. 2 The initial hypotension (-18+/-2.0 mmHg at 1 min) and the tachycardia (110+/-10 b.p.m.) produced by the intrathecal (i.t.) injection of the stable NK(1) receptor agonist [Sar(9), Met(O(2))(11)]-SP (Sar9, 0.65 nmol) at T-9 spinal cord level was inhibited by the prior injection of 65 nmol LY306740 or LY303870 (NK(1) receptor antagonists). No inhibition was seen when a similar dose of antagonists was given intravenously. 3 The prior i.t. injection of the GABA(B) receptor antagonist CGP52432 (100 nmol) reduced the hypotension evoked by Sar9 (0.65 nmol) and by the GABA(B) receptor agonist baclofen (100 nmol). The GABA(A) receptor antagonist bicuculline (25 nmol, i.t.) was without effect against Sar9, and the GABA(A) agonist muscimol (100 nmol, i.t.) had no cardiovascular effect. 4 The putative involvement of other mediators (dopamine, serotonine, glycine and glutamate) in Sar9-induced hypotension was made unlikely on the basis of various pharmacological treatments. Thus data, suggest that the transient hypotension which occurs upon the activation of NK(1) receptors in the spinal cord is due to the release of GABA which in turn activates GABA(B) receptors to inhibit sympathetic pre-ganglionic fibres. This mechanism may have a physiological significance in the spinal reflex autonomic control of arterial blood pressure.
Brouillette
Jonathan
J
Department of Physiology, Faculty of Medicine, Université de Montréal C.P. 6128, Succursale Centre-ville, Québec, Canada, H3C 3J7.
Couture
Réjean
R
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D010721:Phosphinic Acids / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001596:Benzylamines; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; D018040:Receptors, Neurokinin-1; D014662:Vasoconstrictor Agents; C062618:substance P, Sar(9)-Met(O2)(11)-; C083008:CGP 52432; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline