Ventilation-induced pulmonary vasodilation at birth is modulated by potassium channel activity.
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 O2 concentrations (designed to maintain normal fetal blood gas tensions) and 2) mechanical ventilation with high inspired O2 concentrations. Tetraethyl-ammonium (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 O2 concentration (FIO2) for 60 min, followed by 1.0 FIO2 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 FIO2; Gli had no effect. These results support the hypothesis that non-ATP-sensitive K+ channels modulate the transition from fetal to neonatal pulmonary circulation.
Tristani-Firouzi
M
M
Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
Martin
E B
EB
Tolarova
S
S
Weir
E K
EK
Archer
S L
SL
Cornfield
D N
DN
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005260:Female; D005333:Fetus / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D007743:Labor, Obstetric; D010100:Oxygen; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012119:Respiration; D012121:Respiration, Artificial; D012756:Sheep / Q000196:embryology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014666:Vasomotor System / Q000196:embryology / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D010100:Oxygen; D005905:Glyburide