sq-29548 and 2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic-acid

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acrylates; Animals; Arachidonic Acid; Arachidonic Acids; Bridged Bicyclo Compounds, Heterocyclic; Cats; Dinoprost; Fatty Acids, Unsaturated; Hydrazines; Lung; Methacrylates; Prostaglandin Endoperoxides, Synthetic; Respiratory Function Tests; Thromboxane A2; Thromboxane-A Synthase

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)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Bridged Bicyclo Compounds, Heterocyclic; Dinoprostone; Endothelium; Epoprostenol; Fatty Acids, Unsaturated; Hydrazines; Indomethacin; Male; Methacrylates; Muscle, Smooth, Vascular; Prostaglandins E; Rats; Rats, Inbred Strains

Administration of the thromboxane A2 (TXA2) synthase inhibitor OKY 1581 to rats significantly increased the urine output elicited by the loop diuretic frusemide. The administration of the TXA2 receptor antagonist SQ 29548 significantly increased the diuretic effect of frusemide. Another TXA2 receptor antagonist L-640,035 increased significantly the diuretic effect of frusemide. Both the sodium excretion rate and urine osmolar excretion rate were significantly increased in rats treated with the TXA2 synthase inhibitor OKY 1581 and frusemide. The data suggest that TXA2 is released during frusemide-induced diuresis in rats, and the released TXA2 has an opposing antidiuretic effect. Key words: antidiuretic hormone, frusemide diuresis, thromboxane inhibitor and antagonists.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Dibenzothiepins; Diuresis; Drug Synergism; Fatty Acids, Unsaturated; Furosemide; Hydrazines; Male; Methacrylates; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium; Thromboxane A2; Thromboxane-A Synthase