Hypotensive and bradycardic effects elicited by spinal dopamine receptor stimulation: effects of D1 and D2 receptor agonists and antagonists.
In anesthetized rats, intrathecal (i.t.) administration, at the upper thoracic level of the spinal cord of fenoldopam (a selective dopamine D1-receptor agonist) or quinpirole (a selective D2-receptor agonist) decreased blood pressure (BP) and heart rate (HR) in a dose-dependent manner. Apomorphine, a nonselective DA receptor agonist, produced similar effects. Apomorphine-induced hypotension was competitively antagonized by either SCH 23390 or remoxipride, selective D1- and D2-receptor antagonists, respectively, but only remoxipride antagonized the bradycardia. Furthermore, SCH 23390 antagonized the hypotensive effect of fenoldopam but did not change that induced by quinpirole. Remoxipride antagonized the hypotensive effect of quinpirole but did not alter the hypotensive effect of fenoldopam. Quinpirole-induced bradycardia was antagonized only by remoxipride. Bradycardia elicited by fenoldopam did not appear to be generated by dopamine receptor stimulation, as suggested by the lack of blocking effects of SCH 23390 and remoxipride. Data obtained with fenoldopam were corroborated with use of SK&F 38393, another dopamine D1-receptor agonist. We conclude that hypotensive effects of i.t.-administered DA receptor agonists appear to result from activation of spinal D1- and D2-receptors whereas bradycardia is related only to activation of spinal D2-receptors.
Pellissier
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G
Laboratoire de Physiologie Pharmacologie II, URA CNRS 1287, Faculté de Pharmacie, Université Joseph Fourier, Grenoble, France.
Demenge
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P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology; D018818:Fenoldopam; D006339:Heart Rate / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017330:Remoxipride; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D014150:Antipsychotic Agents; D001549:Benzamides; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017330:Remoxipride; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018818:Fenoldopam; D001058:Apomorphine