Adenine nucleotides but not pyridine coenzymes are involved in the
opening of atp sensitive k+ channels of hypoxic rat pulmonary
arteries.
Shigemori, Kazuo, Takeshi Ishizaki, Shigeru Matsukawa, Akio Sakai,
Tsuguhiko Nakai, and Susumu Miyabo.
Third Dept. of Internal Medicine, Fukui Medical School, Fukui,
Japan. 910-11, Central Research Laboratories, Fukui Medical School,
Fukui, Japan. 910-11, Dept. of Environmental Physiology, School of
Medicine Sinsyu University, Matsumoto, Japan. 390
APStracts 2:0222L, 1995.
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-dependent K+
channel blocker, glibenclamide (concentration over 1 M) or
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 HPLC 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/ADP ratio, and increased the ADP and the
AMP content in association with a rapid increase in the NADH and the
NADH/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/ADP ratio) but did not affect the
hypoxia-induced changes of the NADH and the NADH/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-dependent K+ channel activation
during hypoxic vasorelaxation.
Received 3 April 1995; accepted in final form 30 November 1995.
APS Manuscript Number L101-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95