ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs

Charles M. Wiener, Alice Dunn, J. T. Sylvester

Research output: Contribution to journalArticle

Abstract

In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 < 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 × 10-7 M) which was reversed by glibenclamide (IC50 = 8 × 10-7 M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs ([glucose] < 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14±0.4 mM had the same effect. As a result, initial Vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCI, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events.

Original languageEnglish (US)
Pages (from-to)500-504
Number of pages5
JournalJournal of Clinical Investigation
Volume88
Issue number2
DOIs
StatePublished - Aug 1991

Keywords

  • Cromakalim
  • Glibenclamide
  • Hypoxia
  • Pulmonary vascular resistance
  • Pulmonary vasoconstriction
  • Sulfonylurea

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'ATP-dependent K<sup>+</sup> channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs'. Together they form a unique fingerprint.

  • Cite this