Role of ATP-sensitive potassium channels in ovine fetal pulmonary vascular tone.
To study the potential role of ATP-sensitive K+ (K+ATP) channels in fetal pulmonary vasoregulation, we studied the effect of a K+ATP channel agonist, lemakalim, and antagonist, glibenclamide, on the fetal pulmonary circulation in nine chronically instrumented late-gestation fetal lambs. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer. Brief (10 min) infusions of lemakalim at 3, 10, and 30 micrograms/min into the LPA produced dose-dependent increases in flow from 68 +/- 7 to 96 +/- 11, 160 +/- 15, and 204 +/- 34 ml/min, respectively. The duration of pulmonary vasodilation after the 10-min infusions of lemakalim at 3, 10, and 30 micrograms/min was 20 +/- 3, 47 +/- 10, and 55 +/- 15 min, respectively. Pulmonary blood pressure and flow did not change with intrapulmonary infusion of glibenclamide (10 mg), a K+ATP channel antagonist. Lemakalim-induced pulmonary vasodilation was not affected by nitro-L-arginine (10 mg), a competitive inhibitor of endothelium-dependent relaxing factor, but was blocked by glibenclamide. Prolonged (2 h) intrapulmonary infusions of lemakalim (2-6 micrograms/min) increased pulmonary blood flow by 137%. The increase in pulmonary blood flow was sustained throughout the infusion. Systemic and pulmonary arterial pressures decreased during prolonged infusion. We conclude that K+ATP channels are present in the fetal pulmonary circulation, but do not participate in the regulation of basal pulmonary vascular tone. K+ATP channel activation produces sustained vasodilation that is not mediated by endothelium-derived relaxing factor. We speculate that birth-related stimuli activate K+ATP channels to enhance the pulmonary vasodilation that occurs at birth.
Cornfield
D N
DN
Department of Pediatrics Children's Hospital, Denver, Colorado.
McQueston
J A
JA
McMurtry
I F
IF
Rodman
D M
DM
Abman
S H
SH
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005333:Fetus / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D019335:Nitroarginine; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D012756:Sheep; D014666:Vasomotor System / Q000187:drug effects / Q000196:embryology*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D019335:Nitroarginine; D000255:Adenosine Triphosphate; D001120:Arginine; D005905:Glyburide