Angiotensin converting enzyme inhibitors (captopril, CGS14831 and CGS14824A) antagonise in vitro smooth muscle prostanoid synthesis: evidence for calcium channel blockade

The present study investigated the effect of the angiotensin-converting enzyme (ACE) inhibitors, captopril, CGS14824A and CGS14831 on in vitro rat aortic and urinary bladder prostacyclin (PGI₂; measured as 6-oxo-PGF_1α by radioimmunoassay) synthesis. PGI₂ synthesis was stimulated with adrenaline (aorta), carbachol (bladder), calcium ionophore A23187, arachidonate and trauma. The ACE inhibitors antagonised adrenaline-, carbachol- and A23187-stimulated PGI₂ synthesis in the aorta and bladder (CGS14824A>captopril>CGS14831) but were without effect on trauma- or arachidonate-stimulated PGI₂ synthesis. The patterns of inhibition of these ACE inhibitors, using the same stimulatory regimes, was very similar to those previously observed by us with known calcium channel blockers (nifedipine, verapamil). These data suggest that: (i) ACE inhibitors possess calcium channel blocking properties, which may be of relevance to the antihypertensive action of these drugs; and (ii) ACE inhibitors did not stimulate vascular PGI₂ synthesis as has been previously suggested.