Role of calcium-activated potassium channels and cyclic nucleotides on pulmonary vasoreactivity to serotonin.
The role of Ca(2+)-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 Ca(2+)-activated K+ channels, significantly potentiated the pressor 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 Ca(2+)-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 Ca(2+)-activated K+ channels and that activation of these specific K+ channels attenuates the pressor response to serotonin. Thus an important relationship appears to exist between the cAMP second messenger system and Ca(2+)-activated K+ channels in canine pulmonary vasoreactivity.
Barman
S A
SA
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912, USA.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008168:Lung / Q000098:blood supply; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D012701:Serotonin / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D013757:Tetraethylammonium Compounds; C016276:8-bromocyclic GMP; D012701:Serotonin; D003994:Bucladesine; D019789:Tetraethylammonium; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine