Ventilation-induced pulmonary vasodilation at birth is modulated by potassium channel activity
Tristani-Firouzi, M.; Martin, E.B.; Tolarova, S.; Weir, E.K.; Archer, S.L.; Cornfield, D.N.
American Journal of Physiology 271(6 Pt 2): H2353-H2359
1996
ISSN/ISBN: 0002-9513 PMID: 8997293 Document Number: 457640
At birth, pulmonary blood flow rapidly increases 8- to 10-fold, and pulmonary arterial pressure falls by 50% within 24 h. The postnatal adaptation of the pulmonary circulation is mediated, in part, by endothelium-derived nitric oxide (EDNO). Recent studies suggest that EDNO may reduce vascular resistance, in part, by activating K+ channels. We hypothesized that K+ channels modulate the changes in pulmonary hemodynamics associated with birth. To test this hypothesis, we studied the effect of K+ channel inhibition on two separate, but interdependent stimuli: 1) mechanical ventilation with low inspired O-2 concentrations (designed to maintain normal fetal blood gas tensions) and 2) mechanical ventilation with high inspired O-2 concentrations. Tetraethylammonium (TEA, 1 mg/min for 100 min; n = 5), a nonspecific K+ channel blocker, glibenclamide (Gli, 1 mg/min for 30 min; n = 6), an ATP-sensitive K+ channel blocker, or saline (n=7) was infused into the left pulmonary artery (LPA) of acutely instrumented fetal lambs. The umbilical-placental circulation remained intact, and lambs were ventilated with 0.10 inspired O-2 concentration (FIO-2) for 60 min, followed by 1.0 Flo, for 20 min. Neither TEA nor Gli had an effect on basal pulmonary tone. TEA attenuated the increase in LPA flow and decrease in pulmonary vascular resistance in response to mechanical ventilation with 0.10 and 1.0 FIO-2; Gli had no effect. These results support the hypothesis that non-ATP-sensitive K+ channels modulate the transition from fetal to neonatal pulmonary circulation.