Alpha 1-adrenoceptor responsiveness in the aging aorta

Eur J Pharmacol. 1995 Feb 14;274(1-3):117-23. doi: 10.1016/0014-2999(94)00717-l.

Abstract

Previous studies from this laboratory have shown that aortic alpha 1-adrenoceptor-mediated responsiveness is altered during maturation and aging. This study examines the possibility that there is a change in the alpha 1-adrenoceptor subtypes in the aorta during maturation and aging. The apparent affinity of norepinephrine, as determined by partial receptor inactivation with the alpha 1-adrenoceptor antagonist phenoxybenzamine, was found to be higher in 1-month-old rats compared to 6- and 24-month-old rats. The alpha 1B-adrenoceptor subtype-selective antagonist chlorethylclonidine was used to examine possible heterogeneity in aortic alpha 1-adrenoceptors. The inhibitory effect of chlorethylclonidine on norepinephrine-stimulated contraction was greater in young animals compared to aged animals. Chlorethylclonidine blocked norepinephrine-stimulated inositol phosphate accumulation in 1-month-old aorta but it produced only partial inhibition in the 6- and 24-month-old aortas. The relatively non-selective alpha 1-adrenoceptor antagonists phenoxybenzamine (0.1 microM) and prazosin (0.1 microM) inhibited inositol phosphate accumulation and contractile responses in all ages. The complete block of alpha 1-adrenoceptor-mediated responses by chlorethylclonidine in younger animals shows that alpha 1-adrenoceptor-mediated responses are mediated by the chlorethylclonidine-sensitive alpha 1-adrenoceptor subtypes. The partial inhibition by chlorethylclonidine of alpha 1-adrenoceptor-mediated responses in 6- and 24-month-old animals indicates an increased role of an alpha 1-adrenoceptor subtype that is relatively insensitive to chlorethylclonidine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Aging / metabolism*
  • Analysis of Variance
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Binding, Competitive
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dose-Response Relationship, Drug
  • Inositol Phosphates / metabolism*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Phenoxybenzamine / pharmacology
  • Rats
  • Rats, Inbred F344
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Adrenergic, alpha-1 / metabolism

Substances

  • Adrenergic alpha-Antagonists
  • Inositol Phosphates
  • Receptors, Adrenergic, alpha-1
  • Phenoxybenzamine
  • chlorethylclonidine
  • Clonidine
  • Norepinephrine