Modifications of canine vascular smooth muscle responses to dihydroergotamine by endogenous prostaglandin synthesis.
Changes in tension were monitored isometrically on spiral strips from canine saphenous veins and arteries. Dihydroergotamine (DHE) (1.7 X 10(-8) M) contracted vein strips about 30% more strongly than arterial strips when the effects were compared to a standard noradrenaline (NA) response. Phentolamine (3.6 X 10(-6) M) reduced the DHE-induced contraction in veins by about 30% and in arteries by about 10%. Indomethacin (2.8 X 10(-7) M) reduced DHE-induced contractions in veins by about 60% but enhanced the DHE effects in the arteries. When arachidonic acid (AA) was added to stimulated vascular strips it caused further contractions in veins but relaxation in arteries. Both effects were inhibited after indomethacin. In veins AA was significantly more effective in the presence of DHE as compared to controls, to NA- or to KCl-stimulated strips. In arteries AA showed the strongest relaxant activity in the presence of NA. Low doses of prostaglandin E2, however, relaxed both venous and arterial strips. The results suggest that contraction of canine vascular smooth muscle is associated with synthesis of a prostaglandin-like substance of substances having constrictor activity in veins but relaxant activity in arteries and that in venous smooth muscle cells the formation of this material is enhanced by dihydroergotamine.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D004087:Dihydroergotamine / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004879:Ergotamines; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D004879:Ergotamines; D011453:Prostaglandins; D011458:Prostaglandins E; D004087:Dihydroergotamine; D011189:Potassium Chloride; D009638:Norepinephrine; D007213:Indomethacin; D010646:Phentolamine