Nafazatrom (BAY g 6575), a potent stimulator of prostacyclin release from cardiac and renal vessel wall.
The enhancement of prostacyclin (PGI2) formation in the cardiac and renal vessel wall by nafazatrom (BAY g 6575) and the vascular effects of this drug were studied in a series of experiments on perfused isolated rat hearts and kidneys. A dose-dependent increase of prostacyclin release (measured as 6-Keto-PGF1 alpha levels, delta % of control) from the vascular endothelium was achieved when nafazatrom was applied in concentrations ranging from 5 X 10(-7) to 10(-5) g/ml. In the heart, the minimal effective dose of nafazatrom was 5 X 10(-7) g/ml causing a 23 delta % increase of PGI2 release; maximal stimulation of PGI2 was 276 delta % at 5 X 10(-6) g/ml nafazatrom. In the kidney, only at the highest concentration of 10(-5) g/ml an increase of PGI2 to 192 delta % was found. Concomitant to the PGI2 release, in both organs, a reduction of perfusion pressure (delta % of control) was observed. Minimal vasodilation in the heart was - 9.6 delta % (5 X 10(-6) g/ml nafazatrom); the maximal effect was - 25.7 delta % (5 X 10(-6) g/ml nafazatrom). In the kidney, the only observed reduction of perfusion pressure was - 12 delta % at 10(-5) g/ml nafazatrom. The cyclooxygenase inhibitor indomethacin (10(-5) g/ml) blocked vasodilation produced by nafazatrom (5 X 10(-6) g/ml); delta P % was 0.5 + 1.
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery / Q000187:drug effects*
D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; D011464:Epoprostenol; C018845:nafazatrom