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1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and 2 Division of Magnetic Resonance Research, Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21224
To assess effects of smooth muscle energy state and intracellular pH (pHi) on pulmonary arterial tone during hypoxia, we measured ATP, phosphocreatine, Pi, and pHi by 31P-NMR spectroscopy and isometric tension in phenylephrine-contracted rings of porcine proximal intrapulmonary arteries. Hypoxia caused early transient contraction followed by relaxation and late sustained contraction. Energy state and pHi decreased during relaxation and recovered toward control values during late contraction. Femoral arterial rings had higher energy state and lower pHi under baseline conditions and did not exhibit late contraction or recovery of energy state and pHi during hypoxia. In pulmonary arteries, glucose-free conditions abolished late hypoxic contraction and recovery of energy state and pHi, but endothelial denudation abolished only late hypoxic contraction. NaCN had little effect at 0.1 and 1.0 mM but caused marked vasorelaxation and decreases in energy state and pHi at 10 mM. These results suggest that 1) regulation of tone, energy state, and pHi differed markedly in pulmonary and femoral arterial smooth muscle, 2) hypoxic relaxation was mediated by decreased energy state or pHi due to hypoxic inhibition of oxidative phosphorylation, 3) recovery of energy state and pHi in hypoxic pulmonary arteries was due to accelerated glycolysis mediated by mechanisms intrinsic to smooth muscle, and 4) late hypoxic contraction in pulmonary arteries was mediated by endothelial factors that required hypoxic recovery of energy state and pHi for transduction in smooth muscle or extracellular glucose for production and release by endothelium.
vascular smooth muscle; endothelium; cyanide; glucose; hypoxic pulmonary vasoconstriction; phosphocreatine; adenosine 5'-triphosphate; phosphate; swine; phosphorus-31 nuclear magnetic resonance
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