Platelet-activating factor stimulates angiotensin converting enzyme activity.
We studied the effects of platelet-activating factor (PAF) on the conversion of angiotensin I to angiotensin II in pulmonary artery endothelial cells. PAF had a novel effect on angiotensin I conversion. The apparent Vmax and Km for angiotensin converting enzyme (ACE) were 2.5 nmol/min per dish and 50 mumol/l, respectively. This activity was enhanced by the addition of PAF to cells. When PAF was added to pulmonary artery endothelial cells, the conversion of angiotensin I to angiotensin II was enhanced about twofold at 10(-6) mol/l PAF. Maximal stimulation was achieved at 10(-5) mol/l PAF. This stimulatory effect was suppressed by ACE inhibitors such as enalapril and PAF antagonist CV3988. When cells were incubated with 10(-6) mol/l PAF, the conversion of angiotensin I to angiotensin II stimulated with PAF was suppressed by CV3988. Enalapril (10(-6) mol/l) completely inhibited the conversion of angiotensin I to angiotensin II in the presence of PAF. Bradykinin also suppressed ACE activity, but phosphatidylcholine and lysophosphatidylcholine did not affect its activity. These results suggest that PAF may have an important role in regulating vascular tone by modulating angiotensin conversion.
Kawaguchi
H
H
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sawa
H
H
Iizuka
K
K
Yasuda
H
H
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010972:Platelet Activating Factor; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A