Factors affecting the termination of cardiovascular actions of 10,10-difluoro,13-dehydroprostacyclin.
Experiments were conducted to determine why 10,10-difluoro,13-dehydroprostacyclin (DF2-PGI2) has a long vascular relaxant activity in vitro but like PGI2 has a short duration of effect in vivo. DF2-PGI2 produced depressor responses in anesthetized dogs which were not affected by nephrectomy suggesting that the kidney was not responsible for the termination of action. DF2-PGI2 given intravenously or into the ascending aorta produced depressor responses of a similar magnitude but injection of the same doses into the hepatic portal circulation resulted in a large attenuation of responses. The data suggest hepatic, but not pulmonary, metabolism of DF2-PGI2. Injection or infusion of PGI2 and DF2-PGI2 into the hindlimb circulation caused vasodilatation of a similar duration suggesting diffusion from tissue sites as another mechanism of termination of action.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D005996:Nitroglycerin / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D011453:Prostaglandins; C024526:10,10-difluoro-13-dehydroprostacyclin; D011464:Epoprostenol; D005996:Nitroglycerin; D000109:Acetylcholine