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 did not affect the NADP+ or the
NADPH content of pulmonary arteries. These findings indicate that an
ATP-sensitive K+ channel regulates the tone of rat pulmonary arteries. Furthermore, an imbalance of the energy state may be involved in
ATP-sensitive K+ channel activation during hypoxic vasorelaxation.