Endothelin-1 (ET-1) causes inhibition of delayed rectifier K+ (KDR) current and constriction in human pulmonary artery (PA)

L. A. Shimoda, G. M. Booth, B. J. Undem, J. T. Sylvester, J. S.K. Sham

Research output: Contribution to journalArticlepeer-review


Recent studies demonstrate that ET-1 constricts human pulmonary vessels. although the mechanism of this response is not completely understood. In this study, we examined possible mechanisms by which ET-1 might constrict human PA. Rings of human intrapulmonary artery (6-14 mm) with and without endothelium (E+ and F-) were suspended in tissue baths containing Kreb's bicarbonate solution (16%O2, 5% CO2; 37°C) for isometric tension recording. Contraction to ET-1 was greater in F- than E+ rings, with maximal response at 10-8M. BQ-123 (10-6 M), an endothelin A (ETA) receptor antagonist, abolished ET-1-induced constriction in both E+ and F- rings. In additional experiments, smooth muscle cells freshly isolated from these arteries were superfused with modified Tyrode's solution and dialyzed with standard high K+ pipette solution. Using whole-cell patch-clamp techniques, outward K+ currents were activated by depolarizing cells from a holding potential of -60 mV to test potentials of -30 to +40 mV. KDR currents were examined in the presence of 100 nM charybdotoxin and were identified by current characteristics and inhibition by 4-aminopyridine (10 mM). ET-1 (10-8 M) caused significant inhibition of KDR current. Staurosporine (1 nM). a protein kinase C (PKC) inhibitor, abolished the effect of ET-1. These data suggest ET-1 constricts human PA via activation of ETA receptors, possibly due to myocyte depolarization via PKC-dependent inhibition of KDR. Furthermore, endothelium-derived relaxing factors modulate this response. Our results are consistent with data we reported previously in the rat. suggesting similar mechanisms may be operative in both species.

Original languageEnglish (US)
Pages (from-to)A344
JournalFASEB Journal
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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