ATP and Adenosine Cause Pulmonary Vasodilation by Stimulation of Different K⁺ Channels in Fetal Lambs. 133

Background: ATP and adenosine are potent pulmonary vasodilators in fetal lambs. We previously reported that release of ATP and adenosine plays a major role in mediating O₂ induced pulmonary vasodilation in fetal lambs. However, the mechanism by which they cause pulmonary vasodilation is unknown. We proposed the hypothesis that ATP and adenosine cause pulmonary vasodilation by activation of K⁺ channels on pulmonary vessels. The objectives of our experiments were to investigate the effects of tetraethyl ammonlum chloride (TEA), a nonspecific K⁺ channel antagonist and 4-aminopyridine (4-AD), a Ca⁺⁺ sensitive K⁺ channel antagonist on pulmonary vascular effects of adenosine, ATP, pinacidil, a known K⁺_ATP channel agonist, and S-nitroso-acetyl-penicillamine(SNAP), an NO donor. Subjects: We instrumented 10 fetal lambs at 122 d gest to measure PVR and pulm flow. Intervention: Control studies were done with infusions of ATP, adenosine, pinacldil and SNAP into left pulmonary artery. These were repeated during continuous infusions of TEA (1 mg/min) or 4-AP (0.4 mg/min). Results: TEA, but not 4-AP inhibited vasodilation caused by pinacidil and SNAP, TEA inhibited the pulmonary vasodilation caused by adenosine but not by ATP. 4-AP inhibited the vasodilation caused by both adenosine and ATP. TEA inhibits K⁺_ATP channels in fetal pulmonary artenes and these channels mediate the effects of NO. Adenosine stimulates both K⁺_ATP and Ca⁺⁺ sensitive K⁺ channels, whereas, ATP stimulates only the Ca⁺⁺ sensitive K⁺ channels. Conclusion: The receptors for adenosine and ATP are coupled to different types of K⁺ channels on pulmonary arteries.