To determine whether K⁺-channel activation mediates shear stress-induced pulmonary vasodilation in the fetus, we studied the hemodynamic effects of K⁺-channel blockers on basal pulmonary vascular resistance and on the pulmonary vascular response to partial compression of the ductus arteriosus (DA) in chronically prepared late-gestation fetal lambs (128-132 days gestation). Study drugs included tetraethylammonium (TEA; Ca²⁺-dependent K⁺-channel blocker), glibenclamide (Glib; ATP-dependent K⁺-channel blocker), charybdotoxin (CTX; preferential high-conductance Ca²⁺-dependent K⁺-channel blocker), apamin (Apa; low-conductance Ca²⁺-dependent K⁺-channel blocker), and 4-aminopyridine (4-AP; voltage-dependent K⁺-channel blocker). Catheters were inserted in the left pulmonary artery (LPA) for selective drug infusion and in the main pulmonary artery, aorta, and left atrium to measure pressure. An inflatable vascular occluder was placed around the DA. LPA flow was measured with an ultrasonic flow transducer. Animals were treated with saline, high- or low-dose TEA, Glib, Apa, CTX, CTX plus Apa, or 4-AP injected into the LPA. DA compression caused a time-related decrease in pulmonary vascular resistance in the control, Glib, Apa, CTX, CTX plus Apa, and low-dose TEA groups but not in the high-dose TEA and 4-AP groups. These data suggest that pharmacological blockade of Ca²⁺- and voltage-dependent K⁺-channel activity but not of low-conductance Ca²⁺- and ATP-dependent K⁺-channel activity attenuates shear stress-induced fetal pulmonary vasodilation.

nitric oxide; potassium channels; pulmonary circulation; blood flow; lambs; endothelium-derived relaxing factor; pulmonary hypertension

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