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-PGF1 alpha 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 greater than captopril greater than 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.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014947:Wounds and Injuries / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001095:Arachidonic Acids; D001552:Benzazepines; D002121:Calcium Channel Blockers; D016718:Arachidonic Acid; D000001:Calcimycin; D002217:Carbachol; D002216:Captopril; D011464:Epoprostenol; C052133:benazeprilat; C044946:benazepril; D004837:Epinephrine