Role of calcium-activated potassium channels and cyclic nucleotides on pulmonary vasoreactivity to serotonin

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15 Scopus citations

Abstract

The role of Ca2+-activated K+ channel modulation and cyclic nucleotide second messenger signal transduction in the canine pulmonary vascular response to serotonin was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured using vascular occlusion techniques. Serotonin (10-5 M) significantly increased precapillary and postcapillary resistance and significantly decreased total vascular compliance by decreasing large vessel compliance and middle compartment compliance. Tetraethylammonium ions (TEA+; 1 mM), an inhibitor of Ca2+-activated K+ channels, significantly potentiated the presser effect to serotonin on both the pulmonary arteries and pulmonary veins. Pretreatment with the guanosine 3',5'-cyclic monophosphate (cGMP)/adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10-5 M), the cell membrane-permeable analog of cAMP, dibutyryl-cAMP (10- 5 M), or the cAMP-dependent vasodilator isoproterenol (10-5 M) inhibited the serotonergic response on both the arteries and veins, which was reversed by TEA+. In contrast, the stable membrane-permeable analog of cGMP, 8- bromo-cGMP (10-5 M), had no effect on serotonin. These results indicate that there is a basal level of vasorelaxation in canine pulmonary blood vessels that is mediated by Ca2+-activated K+ channel activity and that inhibition of these K+ channels increases pulmonary vascular tone and potentiates the pulmonary vasoactive response to serotonin. Also, these data suggest that cAMP-induced pulmonary vasodilation is mediated primarily by Ca2+-activated K+ channels and that activation of these specific K+ channels attenuates the presser response to serotonin. Thus an important relationship appears to exist between the cAMP second messenger system and Ca2+activated K+ channels in canine pulmonary vasoreactivity.

Original languageEnglish (US)
Pages (from-to)L142-L147
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume273
Issue number1 17-1
DOIs
StatePublished - Jul 1997

Keywords

  • 5-hydroxytryptamine
  • Potassium ion channels
  • Pulmonary vascular resistance and compliance
  • Second messenget
  • Tetraethylammonium ions

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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