Characterization of alpha1-adrenoceptor subtypes mediating vasoconstriction in human umbilical vein

Br J Pharmacol. 1999 Jan;126(2):437-42. doi: 10.1038/sj.bjp.0702320.

Abstract

1. The present study attempted to characterize pharmacologically the subtypes of alpha-adrenoceptors mediating contractions in human umbilical vein (HUV). 2. HUV rings were mounted in isolated organ baths and cumulative concentration-response curves were constructed for the alpha-adrenoceptor agonists phenylephrine and adrenaline. Adrenaline was more potent than phenylephrine (pD2=7.29 and 6.04 respectively). 3. Isoproterenol exhibited no agonism on KCl pre-contracted HUV rings. Propranolol (1 microM) and rauwolscine (0.1 microM) did not affect the concentration-response curves to adrenaline. These results demonstrate the lack of involvement of functional beta-or alpha2-adrenoceptors in adrenaline-induced vasoconstriction. 4. The non subtype selective alpha1-adrenoceptor antagonist prazosin was evaluated on phenylephrine and adrenaline concentration-response curves. The effects of the competitive alpha1A and alpha1D-adrenoceptor antagonists, 5-methyl urapidil and BMY 7378 and the irreversible alpha1B selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline concentration-response curves. 5. The potencies of prazosin against responses mediated by adrenaline (pA2= 10.87) and phenylephrine (pA2= 10.70) indicate the involvement of prazosin-sensitive functional alpha1-adrenoceptor subtype in vasoconstriction of the HUV. 6. The potencies of 5-methyl urapidil (pA2 = 6.70) and BMY 7378 (pA2= 7.34) were not consistent with the activation of an alpha1A- or alpha1D-adrenoceptor population. 7. Exposure to a relatively low CEC concentration (3 microM) abolished the maximum response to adrenaline suggesting that this response was mediated by an alpha1B-adrenoceptor subtype. 8. We conclude that HUV express a prazosin-sensitive functional alpha1-adrenoceptor resembling the alpha1B-subtype according with the low pA2 values for both 5-methyl urapidil and BMY 7378 and the high sensitivity to CEC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agonists / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists / pharmacology
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dose-Response Relationship, Drug
  • Epinephrine / pharmacology
  • Humans
  • In Vitro Techniques
  • Phenylephrine / pharmacology
  • Piperazines / pharmacology
  • Prazosin / pharmacology
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Umbilical Veins / drug effects
  • Umbilical Veins / physiology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasoconstrictor Agents / pharmacology

Substances

  • Adrenergic Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • Vasoconstrictor Agents
  • 5-methylurapidil
  • Phenylephrine
  • chlorethylclonidine
  • BMY 7378
  • Clonidine
  • Prazosin
  • Epinephrine