Involvement of GABA and glutamate receptors in the blood pressure responses to intrathecally injected sodium nitroprusside in anesthetized rats.
In pentobarbital-anesthetized rats the intrathecal (i.t.) injection of the nitric oxide (NO) donor, sodium nitroprusside (125, 250 and 500 nmol), induced a dose-dependent hypotensive response followed by a dose-dependent pressor effect. The pressor response to sodium nitroprusside (250 nmol) was reduced to 30% of the control value by the selective antagonist for AMPA/kainate receptors, 6.7-dinitroquinoxaline-2,3-dione (50 nmol, i.t.), whereas it was not modified by the selective NMDA receptor antagonist, 2-amino-5-phosphono-valeric acid (30 nmol, i.t.). The hypotensive effect of sodium nitroprusside was antagonized by the GABA(A) receptor antagonists, bicuculline (4.4 nmol, i.t.) and picrotoxin (4.4 nmol, i.t.), and also by the GABA(B) receptor antagonist, 2-hydroxy saclofen (113 nmol, i.t.). The blood pressure responses to sodium nitroprusside were not modified by blockade of muscarinic receptors with methyl atropine (164 nmol, i.t.), or of nicotinic receptors with hexamethonium (211 nmol, i.t.), of alpha1-adrenoceptors with prazosin (3.1 nmol, i.t.), of alpha2-adrenoceptors with yohimbine (2.8 micromol/kg, i.v.), of 5-HT receptors with methysergide (5.1 micromol/kg, i.v.), or of glycine receptors with strychnine (65 nmol, i.t.). It is concluded that NO generated from sodium nitroprusside in the spinal cord exerts inhibitory and excitatory effects on blood pressure probably through the release of GABA and glutamate, respectively. The inhibitory action on blood pressure involves the stimulation of spinal GABA(A) and GABA(B) receptors whereas the excitatory response to glutamate appears to be mediated through the activation of spinal AMPA/kainate receptors.
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. mgarcia@huemul.ffyb.uba.ar
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Celuch
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide