Mechanism of action of endothelin-1 in the canine pulmonary circulation

Scott A Barman, J. R. Pauly

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Possible mechanisms of action by which endothelin (ET)-1 has an effect on pulmonary vascular resistance and compliance in the canine pulmonary circulation were investigated in the isolated blood-perfused dog lung by use of vascular occlusion techniques. In the present study, ET-1 (10-8 M) increased pulmonary vascular resistance and pulmonary capillary pressure by postcapillary vasoconstriction. In addition, ET-1 decreased total vascular compliance and middle-compartment compliance. Pretreatment with the ET(A) receptor antagonist BQ-610 (10-7 M) or the protein kinase C inhibitors staurosporine (10-6 M) and calphostin C (10-6 M) completely blocked the pressor effect of ET-1. Elimination of extracellular calcium mobilization through voltage-dependent calcium channels by verapamil (10-5 M) or modulation of G protein signal transduction by pertussis toxin challenge (15 μg/kg) had no significant effect on the ET-1-induced pulmonary vascular response. The results of the present study indicate that ET-1 causes pulmonary vasoconstriction in the canine pulmonary circulation through ET(A) receptor mediation and protein kinase C activation, possibly leading to intracellular calcium release. In contrast, the ET-1-induced pulmonary vascular response does not appear to involve extracellular calcium entry through voltage-dependent calcium-channel activation or pertussis toxin- sensitive G protein-signaling mechanisms.

Original languageEnglish (US)
Pages (from-to)2014-2020
Number of pages7
JournalJournal of Applied Physiology
Volume79
Issue number6
DOIs
Publication statusPublished - Jan 1 1995

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Keywords

  • G proteins
  • calcium
  • endothelin A receptors
  • pertussis toxin
  • protein kinase C
  • pulmonary vascular compliance
  • pulmonary vascular resistance
  • vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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