Factors affecting the termination of cardiovascular actions of 10, 10-difluoro, 13-dehydroprostacyclin

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Abstract

Experiments were conducted to determine why 10,10-difluoro, 13-dehydroprostacyclin (DF2-PGI2) has a long vascular relexant activity invitro but like PGI2 hads a short duration of effect invivo. 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 oarta 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 hepatitic, but not pulmonary, metabolism of DF2-PGI2. Injection or infusion of PGI2 and DF2-PGI2 into the hindlimb circulation caused vasodilation of a similar duration suggesting diffusion from tissue sites as another mechanims of termination of action.

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