Critical role of endothelium in sustained arterial contraction during prolonged hypoxia.
Acute anoxia or severe hypoxia causes an initial transient contraction followed by marked relaxation of vascular tissues. We observed a spontaneous gradual sustained contraction of rat aortic rings following relaxation when hypoxia was prolonged. Deendothelialization as well as treatment of the endothelium-intact rings with nitric oxide synthase inhibitors or oxyhemoglobin abolished the late hypoxic contraction despite prolonged hypoxia. The prolonged hypoxia-induced sustained contraction was not affected by adenosine receptor blockade, cyclooxygenase inhibition, free radical scavengers, or the endothelin receptor antagonists. The ATP-sensitive K+ channel blocker glibenclamide abbreviated the duration of hypoxic relaxation and potentiated the magnitude of late hypoxic contraction. These data suggest that the late-sustained hypoxic contraction of arterial tissues is dependent on the presence of intact functional endothelium. Activation of ATP-sensitive K+ channels may participate in the genesis of hypoxic relaxation. However, cyclooxygenase products, free oxygen radicals, adenosine, and endothelin are not involved in the regulation of hypoxia-mediated events in rat aortic rings.
Yang
B C
BC
Department of Medicine, University of Florida 32610.
Mehta
J L
JL
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
D010108:Oxyhemoglobins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D000255:Adenosine Triphosphate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005905:Glyburide; D007213:Indomethacin