MECHANISM OF INCREASED ANGIOTENSIN-CONVERTING ENZYME-ACTIVITY STIMULATED BY PLATELET-ACTIVATING FACTOR

We studied the effects of platelet activating factor (PAF) on angiotensin-converting enzyme (ACE). PAF (1 · 10-10 to 1 · 10-6 M) had a novel effect on angiotensin I conversion. Pulmonary artery endothelial cells converted 1 nmol/dish of 125I-angiotensin I to angiotensin II in the absence of PAF. ACE activity was increased to 2.5 nmol/dish by the addition of 1 · 10-6 M of PAF. To clarify the mechanism of this stimulatory effect of PAF on ACE, Ca2+ influx and inositol 1,4,5-trisphosphate (IP3) release in pulmonary artery endothelial cells were determined. PAF stimulated Ca2+ influx in a dose-dependent manner. PAF also stimulated phospholipase C (PLC) activity and released IP3. To study the relationship between PLC activity and ACE activity, neomycin was added. The Ca2+ influx and IP3 release stimulated by 10-6 M of PAF were suppressed by about 60-70%. ACE activity was also inhibited up to 70% in the presence of PAF (10-10 - 10 M) by 50 M of neomycin. These results suggest that ACE was stimulated by PAF, and that its activityl in endothelial cells may be mediated by the PI-turnover pathway via changes in PLC activity and IP3-mediated Ca2+ release from intracellular stores. © 1990.