Mechanisms of contracting action of oxyhemoglobin in isolated monkey and dog cerebral arteries.
Oxyhemoglobin (HbO2) produced a concentration-dependent contraction of monkey and dog cerebral artery strips, which was significantly attenuated by endothelium denudation. The contractile response was suppressed by treatment with indomethacin, aspirin, and diphloretin phosphate, a prostaglandin (PG) receptor antagonist. OKY 046, a thromboxane synthase inhibitor, attenuated both the contractions caused by HbO2 and PGF2 alpha. Contractions by arachidonic acid (AA) of the monkey arteries were markedly inhibited by indomethacin and moderately attenuated by endothelium denudation. Treatment with superoxide dismutase and catalase failed to reduce the response to HbO2 and AA. The median effective concentration of HbO2 in producing dog cerebral artery contraction was approximately 1,000 times as high as the median inhibitory concentration in inhibiting the effect of endothelium-derived relaxing factor (EDRF) released from dog femoral arteries in response to acetylcholine. It is concluded that contractions caused by HbO2 are not associated with suppression of EDRF released spontaneously from monkey and dog cerebral arteries, but with vasoconstrictor PGs released mainly from endothelium. Thromboxane A2, superoxide anions, and hydrogen peroxide do not appear to be involved.
Toda
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Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002374:Catalase / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008251:Macaca; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009994:Osmolar Concentration; D010108:Oxyhemoglobins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D008689:Methacrylates; D010108:Oxyhemoglobins; D016718:Arachidonic Acid; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; C034364:ozagrel