6-ketoprostaglandin-f1-alpha and 15-hydroperoxy-5-8-11-13-eicosatetraenoic-acid

This study was undertaken to evaluate the effects of acute pressure overload on prostacyclin (PGI2) release and the influences of 15-hydroperoxy-eicosatetraenoic acid (15-HPETE), an inhibitor of PGI2 synthetase, and indomethacin, an inhibitor of cyclo-oxygenase, in canine hearts. Gradual stenosis of the ascending aorta was performed in 24 anesthetized open-chest dogs. The mongrel dogs were divided into three groups, which received indomethacin, 15-HPETE, and no drug. Changes in the hemodynamics, regional myocardial blood flow (MBF) by the method of H2 gas clearance, and plasma immunoreactive 6-keto-prostaglandin (PG) F1 alpha level in the descending aorta (AO) and great cardiac vein (GCV) were measured. Five minutes after aortic stenosis, the plasma immunoreactive 6-keto-PGF1 alpha level in the GCV and MBF increased from 162 +/- 23 to 289 +/- 37 pg/ml and from 87 +/- 5 to 107 +/- 8 ml/min/100 g, respectively, and the calculated coronary vascular resistance (CVR) decreased significantly from 0.93 +/- 0.08 to 0.77 +/- 0.08 mmHg/ml/min/100 g. These significant changes persisted thereafter. Continuous infusion of 15-HPETE (66 pg/kg/min) into the coronary artery simultaneously prevented significant changes in MBF and the plasma immunoreactive 6-keto-PGF1 alpha level in the GCV and CVR. Intravenous infusion of indomethacin (5 mg/kg), on the other hand, induced a significant decrease in the plasma immunoreactive 6-keto-PGF1 alpha level in both the GCV and AO; significant changes in MBF 5 to 15 min after aortic stenosis and CVR were not affected. From these results, it is suggested that PGI2 plays an important role in the regulation of coronary blood flow in canine hearts with acute pressure overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Aortic Valve Stenosis; Arachidonic Acids; Blood Pressure; Coronary Circulation; Dogs; Epoprostenol; Female; Hemodynamics; Leukotrienes; Lipid Peroxides; Male; Vascular Resistance

Aortic rings from rats, rabbits and guinea-pigs produce different amounts of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable breakdown product of prostacyclin, i.e. 2760 +/- 195, 160 +/- 10 and 87 +/- 17 pg 6-oxo-PGF1 alpha per mg wet weight in 30 min. Vitamin C enhances the production of 6-oxo-PGF1 alpha by the aortic tissue of these three species, independent of their basal release. This increase was only significant if vitamin C was present in the preincubation as well as in the incubation fluid. 15-Hydroperoxy-arachidonic acid inhibits the production of 6-oxo-PGF1 alpha (IC50:6 microM) and this inhibitory effect was completely neutralized by vitamin C. The increased production of 6-oxo-PGF1 alpha is not due to an increased release of the substrate arachidonic acid. It is suggested that vitamin C enhances the formation of 6-oxo-PGF1 alpha by protecting the cyclo-oxygenase and PGI-synthase.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acids; Ascorbic Acid; Blood Vessels; Dose-Response Relationship, Drug; Epoprostenol; Guinea Pigs; Leukotrienes; Lipid Peroxides; Male; Rabbits; Rats

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Cattle; Endocardium; Epoprostenol; Heart Valves; Leukotrienes; Lipid Peroxides; Myocardium; Peroxides; Platelet Aggregation; Prostaglandins; Prostaglandins H; Tissue Extracts

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Cyclooxygenase Inhibitors; Digestive System; Dogs; Gastric Mucosa; Intestinal Mucosa; Leukotrienes; Lipid Peroxides; Prostaglandins; Prostaglandins E; Prostaglandins F; Prostaglandins H

Partially purified prostacyclin synthase from pig aorta converted the prostaglandin (PG) endoperoxide PGH2 to prostacyclin (PGI2), and PGH1 to 12-hydroxy-8,10-heptadecadienoic acid (HHD). Both reactions were inhibited by 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HP) in a dose-dependent rashion. However, the reactions PGH2 leads to PGI2 and PGH1 leads to HHD appeared to differ: substrate availability was rate limiting in the latter reaction, while the enzyme became rapidly saturated witth PGH2 and a steady rate of prostacyclin formation was observed at higher substrate levels.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acids; Cytochrome P-450 Enzyme System; Epoprostenol; Fatty Acids, Unsaturated; Hot Temperature; Intramolecular Oxidoreductases; Leukotrienes; Lipid Peroxides; Microsomes; Peroxides; Prostaglandin Endoperoxides; Prostaglandins; Prostaglandins E; Prostaglandins F; Prostaglandins H; Swine