Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits the binding of N-formylmethionyl-leucyl-phenylalanine to neutrophil receptors

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 281; no. 2; pp. 624 - 628
• Main Authors: Raiden, S, Giordano, M, Andonegui, G, Trevani, A S, López, D H, Nahmod, V, Geffner, J R
• Format: Journal Article
• Language: English
• Published: United States 01.05.1997
• Subjects: Angiotensin I - metabolism; Angiotensin Receptor Antagonists; Antihypertensive Agents - pharmacology; Biphenyl Compounds - pharmacology; Humans; Imidazoles - pharmacology; Losartan; N-Formylmethionine Leucyl-Phenylalanine - antagonists & inhibitors; N-Formylmethionine Leucyl-Phenylalanine - metabolism; Neutrophil Activation - drug effects; Neutrophils - drug effects; Neutrophils - metabolism; Receptors, Angiotensin - metabolism; Tetrazoles - pharmacology
• ISSN: 0022-3565

Losartan, a selective antagonist of AT1 receptors for angiotensin II, is widely used clinically to manage hypertension. We report here that losartan markedly inhibits neutrophil shape change, adherence and chemiluminescence responses triggered by N-formylmethionyl-leucyl-phenylalanine (fMLP), without affecting responses induced by immune complexes, zymosan or concanavalin A. Neither saralasin, another antagonist of angiotensin II receptors, nor captopril, an angiotensin-converting enzyme inhibitor, reproduced the effects of losartan. It was also observed that neutrophil responses triggered by fMLP were not affected by exogenously added angiotensin II. The effect of losartan on the binding of fMLP was measured using [3H]fMLP. It was found that losartan inhibits the binding of [3H]fMLP to neutrophil receptors. As observed for neutrophils, studies performed with monocytes showed that losartan inhibits chemiluminescence emission triggered by fMLP, without affecting chemiluminescence responses triggered by immune complexes, zymosan or concanavalin A.