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

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 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.

• Authors: K Shigemori, T Ishizaki, S Matsukawa, A Sakai, T Nakai, S Miyabo
• Journal: The American journal of physiology (Am J Physiol) Vol. 270 Issue 5 Pt 1 Pg. L803-9 (May 1996) ISSN: 0002-9513 [Print] United States
• PMID: 8967515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenine Nucleotides
• Hypoglycemic Agents
• Nucleotides
• Potassium Channels
• Adenosine Triphosphate
• Glyburide

Topics

• Adenine Nucleotides (physiology)
• Adenosine Triphosphate (pharmacology)
• Animals
• Glyburide (pharmacology)
• Hyperglycemia (physiopathology)
• Hypoglycemic Agents (pharmacology)
• Hypoxia (physiopathology)
• In Vitro Techniques
• Male
• Nucleotides (analysis)
• Potassium Channels (drug effects, physiology)
• Pulmonary Artery (chemistry, drug effects, physiopathology)
• Rats
• Rats, Sprague-Dawley