Role of the vascular endothelium in the contractile response to prostacyclin in the isolated rat aorta.
Prostacyclin (PGI2) relaxes vascular smooth muscle in several species but, in high doses, PGI2 has been reported to contract several isolated arteries. Vascular endothelium is known to be obligatory for the vasodilatory responses to acetylcholine and several other substances. We therefore investigated the contractile effect of various prostanoids on rat abdominal aorta in which the endothelium was left intact or was removed. PGI2 (4-2000 ng/ml), 6-keto-prostaglandin (PG) E1, PGE1 and PGE2 (4-800 ng/ml) contracted both intact and de-endothelialized aortic segments in a dose-dependent manner. PGI2 (8-2000 ng/ml) increased the force generated by aortic rings with intact endothelium from 77.3 +/- 24.6 to 685 +/- 99.2 mg. The response to similar doses of PGI2 in aortic rings with the endothelium removed was reduced significantly (22.7 +/- 14.1 to 260 +/- 116.4 mg). This contractile response to PGI2 in both intact and de-endothelialized aortic rings was abolished by indomethacin pretreatment (20 micrograms/ml for 30 min) and was also blocked completely by the thromboxane receptor antagonist SQ 29548 (100 ng/ml). In contrast, the thromboxane synthase inhibitor OKY 1581 (2.5 micrograms/ml) did not significantly reduce the contractile response to PGI2. Unlike PGI2, the force generated by PGE2 (4-800 ng/ml) in aortic rings with intact endothelium (0-550.0 +/- 107.2 mg) was not significantly different from that generated by aortic rings without endothelium (35.0 +/- 23.6 to 650.0 +/- 193.2 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015232:Dinoprostone; D004727:Endothelium / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008689:Methacrylates; D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; C045749:SQ 29548; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin