VENTILATION-INDUCED PULMONARY VASODILATION AT BIRTH IS MODULATED BY POTASSIUM CHANNEL ACTIVITY

At birth, pulmonary blood flow rapidly increases 8- to 10-fold, and pu lmonary arterial pressure falls by 50% within 24 h. The postnatal adap tation of the pulmonary circulation is mediated, in part, by endotheli um-derived nitric oxide (EDNO). Recent studies suggest that EDNO may r educe vascular resistance, in part, by activating K+ channels. We hypo thesized that K+ channels modulate the changes in pulmonary hemodynami cs associated with birth. To test this hypothesis, we studied the effe ct of K+ channel inhibition on two separate, but interdependent stimul i: 1) mechanical ventilation with low inspired O-2 concentrations (des igned to maintain normal fetal blood gas tensions) and 2) mechanical v entilation with high inspired O-2 concentrations. Tetraethylammonium ( TEA, 1 mg/min for 100 min; n = 5), a nonspecific K+ channel blocker, g libenclamide (Gli, 1 mg/min for 30 min; n = 6), an ATP-sensitive K+ ch annel blocker, or saline (n = 7) was infused into the left pulmonary a rtery (LPA) of acutely instrumented fetal lambs. The umbilical-placent al circulation remained intact, and lambs were ventilated with 0.10 in spired O-2 concentration (FIO2) for 60 min, followed by 1.0 FIO2 for 2 0 min. Neither TEA nor Gli had an effect on basal pul;nonary tone. TEA attenuated the increase in LPA flow and decrease in pulmonary vascula r resistance in response to mechanical ventilation with 0.10 and 1.0 F IO2; Gli had no effect. These results support the hypothesis that non- ATP-sensitive K+ channels modulate the transition from fetal to neonat al pulmonary circulation.