title: Vascular alpha 1D-adrenoceptors have a role in the pressor response to phenylephrine in the pithed rat.
abstract: In rats, the pressor response to intravenous (i.v.) phenylephrine is mediated by vascular alpha 1A- and alpha 1B-adrenoceptors, but the role of alpha 1D-adrenoceptors is uncertain. These studies evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4,5]decane-7,9-dio ne 2HCl), on the pressor effect to i.v. phenylephrine (alpha 1A/B/D-adrenoceptor agonist) and (R)A-61603 (alpha 1A-adrenoceptor agonist; N-[5-(4,5-dihydro-1 H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-l -yl] methanesulfonamide HBr) in pithed rats. Pretreatment with BMY 7378 (0.1-1 mg/kg) competitively antagonized the phenylephrine pressor response, but not the (R)A-61603 pressor curve. At 10 mg/kg, BMY 7378 antagonized the (R)A-61603 response, indicating the non-selective blockade of alpha 1A-adrenoceptors. These findings demonstrate that i.v. phenylephrine can activate vascular alpha 1D-adrenoceptors in the pithed rat.
authors.affiliation: Hoechst Marion Roussel Pharmaceuticals, Inc., Somerville, NJ 08876, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: H M
authors.initials: HM
authors.lastname: Vargas
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: C094643:A 61603; C547721:Adra1d protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D013764:Tetrahydronaphthalenes; C057446:5-methylurapidil; D010656:Phenylephrine; C053428:BMY 7378