Evidence for stimulation of neutrophil degranulation by selected angiotensin converting enzyme inhibitors in vitro.
Polymorphonuclear neutrophils (PMN) participate in the development of myocardial injury during ischaemia/reperfusion and granules released by human neutrophils contain proteases capable of activating prorenin in human plasma and can cleave angiotensin II directly from angiotensin I and angiotensinogen. The purpose of the present study was to investigate whether angiotensin converting enzyme (ACE)-inhibitors exert an in vitro effect on PMN degranulation. Isolated neutrophils were incubated with captopril, lisinopril, enalaprilat or ramiprilat and release of lysozyme and myeloperoxidase was measured from unstimulated and opsonised zymosan stimulated cells. All ACE inhibitors increased neutrophil myeloperoxidase release and lysozyme release by both unstimulated and stimulated cells. In the presence of saline unstimulated PMN released 4.48 +/- 0.68% and zymosan-stimulated cells released 7.28 +/- 0.76% of myeloperoxidase content and the enzyme release increased after incubation with captopril (5.55 +/- 0.71 and 8.74 +/- 0.72%), lisinopril (5.43 +/- 0.57 and 9.02 +/- 0.7%), enalaprilat (6.05 +/- 0.67 and 9.20 +/- 0.82%) and ramiprilat (5.82 +/- 0.69 and 9.26 +/- 0.74%), respectively. In the presence of saline unstimulated PMN released 16.71 +/- 1.28% and zymosanstimulated PMN released 34.42 +/- 1.71% of lysozyme content and the release increased after incubation with captopril (21.15 +/- 1.36 and 42.75 +/- 1.95%), lisinopril (23.95 +/- 1.26 and 39.23 +/- 1.94%), enalaprilat (21.34 +/- 1.32 and 41.59 +/- 1.99%) and ramiprilat (20.88 +/- 1.35 and 37.53 +/- 1.95%) by unstimulated PMN, respectively. The ACE-inhibitory effect of these drugs may therefore be decreased by stimulation of PMN degranulation and neutrophil-dependent angiotensin II forming pathway.
Miselis
J
J
Academy of Medicine, Department of Intensive Therapy, Poznan, Poland.
Siminiak
T
T
Wysocki
H
H
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D015773:Enalaprilat / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000097:blood*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D009195:Peroxidase / Q000097:blood*; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D013053:Spectrophotometry; D015054:Zymosan / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; D015054:Zymosan; D002216:Captopril; D017706:Lisinopril; D009195:Peroxidase; D009113:Muramidase; D015773:Enalaprilat; D017257:Ramipril