Adenine nucleotides via activation of ATP-sensitive K+ channels modulate hypoxic response in rat pulmonary artery.
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.
Shigemori
K
K
Third Department of Internal Medicine, Fukui Medical School, Japan.
Ishizaki
T
T
Matsukawa
S
S
Sakai
A
A
Nakai
T
T
Miyabo
S
S
D000227:Adenine Nucleotides / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009711:Nucleotides / Q000032:analysis; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000227:Adenine Nucleotides; D007004:Hypoglycemic Agents; D009711:Nucleotides; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide