Functional comparison of endothelin receptors in human and rat pulmonary artery smooth muscle

Am J Physiol. 1997 Feb;272(2 Pt 1):L211-8. doi: 10.1152/ajplung.1997.272.2.L211.

Abstract

The receptors mediating arterial smooth muscle contraction to endothelins (ET) differ among species and origin of vascular bed. We characterized ET receptors mediating contraction of endothelium-denuded human intralobar pulmonary artery (hIPA) and rat intralobar (rIPA) and extralobar left branch (rLPA) pulmonary artery with ET-1, ET-2, ET-3, sarafotoxin S6c, sarafotoxin S6b, and ET receptor antagonists in vitro. Rat aorta was studied for comparison. Each vascular segment showed concentration-dependent contraction with a rank order sensitivity (pD2) profile of ET-1 > or = ET-2 = sarafotoxin S6b > ET-3. Maximum contraction to ET-1 was greater than to sarafotoxin S6c in all preparations. Responses of rIPA and rLPA to sarafotoxin S6c were conspicuous when compared with hIPA or aorta. The ET(A) receptor blockers BQ-123 and BMS-182874 competitively antagonized ET-1 responses of hIPA and aorta, but not rLPA. The ET(B) receptor antagonist BQ-788 attenuated contractions of rIPA and rLPA to ET-3 and sarafotoxin S6c, respectively. In conclusion, ET(B)-mediated contraction of endothelium-denuded conduit pulmonary arteries varies among species and may contribute more to contraction of rIPA and rLPA than of hIPA and aorta, although maximum ET(B)-mediated contraction is smaller than that mediated by the ET(A) receptor.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Dansyl Compounds / pharmacology
  • Endothelin Receptor Antagonists
  • Humans
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism*
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Piperidines / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism*
  • Rats / metabolism*
  • Rats, Sprague-Dawley
  • Receptors, Endothelin / metabolism*

Substances

  • Dansyl Compounds
  • Endothelin Receptor Antagonists
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Receptors, Endothelin
  • 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide
  • BQ 788
  • cyclo(Trp-Asp-Pro-Val-Leu)