Endothelium-dependent and independent responses to prostaglandin H2 and arachidonic acid in isolated dog cerebral arteries.
The addition of prostaglandin (PG) H2 produced a transient contraction followed by a relaxation in helical strips of dog cerebral arteries partially contracted with PGF2 alpha or K+. The contraction was abolished by removal of endothelium, and the relaxation was potentiated. Relaxation induced by PGI2 was not influenced by endothelium denudation. The PGH2-induced contraction in strips with intact endothelium was not influenced by OKY-046, a thromboxane A2 synthesis inhibitor, but was abolished by treatment with ONO3708, an antagonist of vasoconstrictor PGs, whereas the relaxation was inhibited by tranylcypromine or diphloretin phosphate, a nonselective PG antagonist. Contraction induced by arachidonic acid (AA) was reversed to relaxation by removal of endothelium or treatment with ONO3708. Treatment with indomethacin attenuated the AA-induced contraction in the intact strips and also the relaxation in the strips treated with ONO3708 or denuded of endothelium. It may be concluded that vasoconstrictor PGs are synthesized from PGH2 or AA mainly in endothelium, and the production of PGI2 from PGH2 is not dependent on endothelium. Thromboxane A2 in concentrations sufficient to elicit significant contractions does not appear to be liberated from the cerebroarterial wall stimulated by PGH2.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D044262:Prostaglandin H2; D011460:Prostaglandins F / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; C049855:ONO 3708; D015237:Dinoprost; D011188:Potassium; D007213:Indomethacin