Involvement of brain 5-HT1A receptors in the hypotensive response to urapidil.
Stimulation of serotonin-1A (5-hydroxytryptamine) (5-HT1A) receptors in the brain stem has been suggested to contribute to the antihypertensive action of the alpha 1-adrenoceptor antagonist urapidil. This hypothesis was tested by analyzing the influence of the 5-HT1A receptor antagonist spiroxatrine on the hypotensive responses to urapidil and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Chloralose/urethane-anesthetized cats underwent thoracotomy and were artificially ventilated. Blood pressure was monitored in the femoral artery. Urapidil (0.01 to 10 mumol/kg) or 8-OH-DPAT (3 to 30 nmol/kg) was injected into a femoral vein and the maximal hypotensive response recorded. A dose-response test with both drugs was performed before and after administration of spiroxatrine (3 and 10 nmol/kg); the latter was given through the vertebral artery, thus delivering the antagonist to the brain stem. Blood pressure was dose-dependently reduced by urapidil and 8-OH-DPAT after intravenous injection. Central administration of spiroxatrine through the vertebral artery shifted the dose-response curves of both drugs markedly and in a dose-dependent manner to the right, while the hypotensive response to the peripheral vasodilator nitroglycerin remained unchanged. The results suggest that the hypotensive response after peripheral administration of urapidil is mediated in part by stimulation of brain 5-HT1A receptors and this effect on central cardiovascular regulation is additive to the blood pressure reduction resulting from peripheral alpha-adrenoceptor blockade.
Kolassa
N
N
Department of Pharmacology, Byk Gulden Pharmaceuticals, Konstanz, Federal Republic of Germany.
Beller
K D
KD
Sanders
K H
KH
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D004146:Dioxanes; D010879:Piperazines; D011985:Receptors, Serotonin; D013141:Spiro Compounds; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015568:urapidil; C018387:spiroxatrine