Vascular Alpha 1D-adrenoceptors Have a Role in the Pressor Response to Phenylephrine in the Pithed Rat

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.