Calcium utilization coupled to stimulation of postjunctional alpha-1 and alpha-2 adrenoceptors in isolated human resistance arteries

J Pharmacol Exp Ther. 1992 Feb;260(2):637-43.

Abstract

Human s.c. resistance arteries (internal diameters 158-353 microns) were mounted in a microvascular myograph, and experiments were designed to examine the calcium pools utilized by selective stimulation of alpha-1 and alpha-2 adrenoceptors. In a concentration-dependent manner, phenylephrine and B-HT 933 evoked contractions mediated by alpha-1 and alpha-2 adrenoceptors, respectively, both in calcium-containing and in calcium-free saline. With respect to the maximum response to potassium in calcium-containing saline, the maximum responses to phenylephrine and B-HT 933 were 96 +/- 6 and 85 +/- 8%, respectively, in calcium-containing saline, and 79 +/- 4 and 14 +/- 2%, respectively, in calcium-free saline. A qualitatively similar difference in maximum responses to alpha-1 vs. alpha-2 adrenoceptor stimulation in calcium-free saline was demonstrated for norepinephrine in the presence of antagonists selective for the two alpha adrenoceptor subtypes. The maximum relaxation in calcium-containing saline produced by the calcium antagonist nitrendipine was 52 +/- 3% in vessels precontracted with phenylephrine, but 80 +/- 5% in vessels precontracted with B-HT 933. A quantitative difference in receptor reserves was demonstrated between alpha-1 and alpha-2 adrenoceptors; 90% of the maximum response was obtained at 34 +/- 5 and 57 +/- 8% receptor occupation, respectively. These data suggest that compared to responses mediated by stimulation of postjunctional alpha-1 adrenoceptors, stimulation of postjunctional alpha-2 adrenoceptors relies heavily on calcium influx. Stimulation of postjunctional alpha-2 adrenoceptors is, however, also coupled to intracellular release of calcium in isolated human s.c. resistance arteries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adult
  • Aged
  • Arteries / drug effects*
  • Arteries / physiology
  • Azepines / pharmacology
  • Calcium / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Nitrendipine / pharmacology
  • Norepinephrine / pharmacology
  • Phenylephrine / pharmacology
  • Receptors, Adrenergic, alpha / drug effects*

Substances

  • Adrenergic alpha-Antagonists
  • Azepines
  • Receptors, Adrenergic, alpha
  • Phenylephrine
  • Nitrendipine
  • azepexole
  • Calcium
  • Norepinephrine