MECHANISM OF THE ACTION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON AGONIST-INDUCED CA2+ INFLUX

To evaluate the direct effects of the angiotensin-converting enzyme (A CE) inhibitors, captopril, enalaprilat, enalapril (a prodrug without t herapeutically significant ACE inhibitory effect) and ramiprilat, on c ellular calcium metabolism, the cytosolic free calcium concentration w as measured in cultured rat vascular smooth muscle cells using the flu orescent dye, fura-2. Preincubation with captopril, enalaprilat, enala pril, or ramiprilat for 40 min significantly reduced the angiotensin I I-induced transplasma membrane calcium influx but did not influence th e angiotensin II-induced calcium release from internal stores. Captopr il and ramiprilat also inhibited arginine vasopressin, but not the tha psigargin-, norepinephrine-, or the BayK 8644-induced changes in cytos olic calcium. Phorbol 12-myristate 13-acetate pretreatment for 30 s ca used an increase in the angiotensin II-induced rise in cytosolic calci um. Although both captopril and verapamil reduced responses to angiote nsin II to similar extents, only verapamil blocked the ability of phor bol 12-myristate 13-acetate to enhance responses to angiotensin II. It is concluded that ACE inhibitors modulate the effects of some but not all agonist-induced transplasma membrane calcium influx.