Prostacyclin generation by cultured human vascular endothelial cells with reference to angiotensin I-converting enzyme.
Prostacyclin (PGI2) generation has been known to be regulated by several endogenous vasoactive substances, and in this study the relationship between angiotensin I-converting enzyme (ACE) related substances and PGI2 generation was investigated using cultured human vascular endothelial cells. Addition of angiotensin I (AI) or bradykinin (BK) enhanced PGI2 generation and increased the level of ACE activity in the culture medium, while the addition of ACE inhibitor (captopril) caused a dose dependent suppression of PGI2 generation and ACE activity. The enhancement of PGI2 generation induced by AI or BK was not affected by pretreatment with captopril, and angiotensin II (AII) did not show any effect on either PGI2 generation or ACE activity. Through these experimental results, the conversion of AI to AII by ACE was considered not to cause the enhancement of PGI2 generation. Captopril solely inhibited PGI2 generation and the reported hypothesis that captopril enhances PGI2 generation by the accumulation of AI or BK via inhibition of ACE was not confirmed in this experimental system. Rather, it is proposed that AI or BK induced PGI2 generation may be regulated by the increased breakdown of AI or BK, as an autoregulation mechanism, that is derived from increased ACE activity by AI or BK.
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D001808:Blood Vessels / Q000201:enzymology / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin