Abstract
The role of an ATP-dependent K+ channel (K(ATP)+) relaxation in the porcine pulmonary vasculature from birth to adulthood was investigated in vitro using levcromakalim on isolated, prostaglandin F2α (30 μM)-precontracted conduit arteries (CA), resistance arteries (RA), and veins (PV). Vessels from neonatal pulmonary hypertensive piglets exposed to chronic hypobaric hypoxia (CHH, 51 kPa) for 3 d, either from birth or from 3 d of age were also studied. Levcromakalim relaxed all vessels in a concentration- and glibenclamide-sensitive manner. In normal CA, the maximal extent of relaxation and sensitivity (EC50) increased between birth and 17 d. Endothelium-removal increased EC50 at 17 d only. Indomethacin (10 μM), but not NG-monomethyl-L-arginine (L-NMMA) (30 μM), inhibited relaxation in CA from newborn, 3-d-old, and adult animals. In RA, levcromakalim-induced relaxations did not change during development and endothelium-removal attenuated relaxations in 3-d-old but not in adult animals. At both ages in RA, L-NMMA attenuated relaxations and subsequent addition of L-arginine (1 mM) restored them. In PV, maximal relaxation increased between birth and 6 d with no change of EC50. At all ages, relaxation was partially endothelium-dependent and inhibited by L-NMMA (except in the newborn). Indomethacin only attenuated relaxations in veins from 6- and 17-d-old animals. CHH did not influence relaxant responses in CA and PV but decreased EC50 in RA. Thus K(ATP)+ channel activation caused relaxation from birth onward in all vascular segments with varying endothelium dependence. CHH did not affect relaxation in the large vessels and up-regulated those in RA. These findings indicate a possible role for K(ATP)+ channels during normal adaptation and a potential therapeutic role in the management of pulmonary hypertensive newborn infants.
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Abbreviations
- ACH:
-
acetylcholine
- CA:
-
intrapulmonary conduit arteries
- CHH:
-
chronic hypobaric hypoxia
- EC50:
-
concentration required to obtain half maximal relaxation
- K(ATP)+:
-
ATP-dependent K+ channel
- L-NMMA:
-
NG-monomethyl-L-arginine
- NO:
-
nitric oxide
- PGF2α:
-
prostaglandin F2α
- PSS:
-
physiologic salt solution
- PV:
-
intrapulmonary veins
- RA:
-
pulmonary resistance-sized arteries
- R max :
-
maximal extent of relaxation
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The authors thank Sue Hodgson for expert secretarial assistance and Dr. Alison Hislop for pertinent discussions.
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Supported by the British Heart Foundation.
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Boels, P., Gao, B., Deutsch, J. et al. ATP-Dependent K+ Channel Activation in Isolated Normal and Hypertensive Newborn and Adult Porcine Pulmonary Vessels. Pediatr Res 42, 317–326 (1997). https://doi.org/10.1203/00006450-199709000-00012
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DOI: https://doi.org/10.1203/00006450-199709000-00012
