6-ketoprostaglandin-f1-alpha and Asthma--Exercise-Induced

The influence of OKY-046, which is a thromboxane (TxA2) synthetase inhibitor, was studied in patients with exercise-induced asthma (EIA). When OKY-046 was administered to 11 patients with EIA-positive (EIA+) asthma, 7 patients showed an effect of the inhibition of airway contraction. As the mechanism of action, inhibition of TxA2 production and acceleration of PGI2 were considered, since OKY-046 has no bronchodilation action. In other words, the fact that TxA2 was a mediator of EIA had been made clear, but it was also found that it had no association as a mediator of leukotrienes (LTC4 and LTB4) in EIA.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Asthma, Exercise-Induced; Drug Evaluation; Exercise Test; Female; Humans; Leukotriene B4; Male; Methacrylates; SRS-A; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Plasma levels of arachidonic acid metabolites, such as thromboxane A2 (TXA2), prostacyclin (PGI2) and leukotrienes (LTS) were measured in patients with exercise-induced asthma (EIA). Asthmatic patients were exercised by treadmill. Before, immediately after and at 5, 15 and 30 minutes after exercise, pulmonary function tests were performed and peripheral venous blood was collected at the indicated times. Plasma TXB2 levels rose after exercise, and this tendency was stronger in EIA negative patients than in EIA positive patients. Plasma 6-keto-PGF1 alpha levels rose slightly after exercise in both EIA positive and negative patients. Plasma LTC4 levels were almost unchanged after exercise in EIA positive patients. Plasma LTC4 levels rose after exercise in EIA negative patients, though the value was always higher in EIA positive patients than in EIA negative patients. Plasma LTB4 levels in both EIA positive and negative patients increased slightly till 5 minutes after exercise, then decreased, and then tended to rise again. Plasma LTB4 levels were higher in EIA positive patients than in EIA negative patients at all times. The ratio of TXB2 to 6-keto-PGF1 alpha after exercise rose more remarkably in EIA negative patients than in EIA positive patients. From these results, we suspected that the metabolites of arachidonic acid may contribute less to chemical mediators of EIA, but the arachidonic acid products of EIA positive patients activated rather towards lipoxygenase cascade than EIA negative patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Arachidonic Acids; Asthma; Asthma, Exercise-Induced; Female; Humans; Leukotrienes; Male; Thromboxane B2