Adenine nucleotides via activation of ATP-sensitive K+ channels modulate hypoxic response in rat pulmonary artery

The American Journal of Physiology
K ShigemoriS Miyabo

Abstract

We examined the role of ATP-sensitive K+ channels in hypoxic pulmonary vasoconstriction, using isolated rat pulmonary arterial rings. Isolated rat pulmonary arterial rings displayed a rapid contraction followed by relaxation under hypoxic conditions. The ATP-sensitive K+ channel blocker glibenclamide (concentration > 1 microM) or a hyperglycemic buffer (15 mM glucose) attenuated the hypoxic relaxation in a dose-dependent manner but did not affect the hypoxia-induced contraction. To examine the relationship between hypoxia, energy, and redox state, intracellular levels of adenine nucleotides and pyridine coenzymes were determined by high-performance liquid chromatography in freeze-dried isolated rat pulmonary arteries at three time points (0, 4, and 10 min) before and during hypoxia. Hypoxia time dependently decreased the ATP content and the ATP-to-ADP ratio and increased the ADP and the AMP content in association with a rapid increase in the NADH and the NADH-to-NAD+ ratio. Hyperglycemic buffer (15 mM glucose) suppressed the hypoxia-induced changes of the adenine nucleotides (the decrease of the ATP content and the ATP-to-ADP ratio) but did not affect the hypoxia-induced changes of the NADH and the NADH-to-NAD+ ratio. Hypoxia d...Continue Reading

Citations

Jul 9, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Michael S WolinSachin A Gupte
Dec 5, 2008·American Journal of Physiology. Cell Physiology·Hélène KleinRémy Sauvé
Feb 3, 2012·Physiological Reviews·J T SylvesterJeremy P T Ward
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Qinghong ZhangRichard H Goodman

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