Vascular alpha 1D-adrenoceptors have a role in the pressor response to phenylephrine in the pithed rat

Eur J Pharmacol. 1996 Jun 3;305(1-3):173-6. doi: 10.1016/0014-2999(96)00229-4.

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.

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Imidazoles / pharmacology
  • Male
  • Phenylephrine / pharmacology*
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Tetrahydronaphthalenes / pharmacology

Substances

  • A 61603
  • Adra1d protein, rat
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Imidazoles
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • Tetrahydronaphthalenes
  • 5-methylurapidil
  • Phenylephrine
  • BMY 7378