No effect of carvedilol on nitric oxide generation in phagocytes but modulation of production of superoxide ions

Since carvedilol has been claimed to possess antioxidative effects, this dr ug might affect functional responses, including nitric oxide (NO) generatio n, of polymorphonuclear neutrophils (PMN) and macrophages. When we assessed the effects of carvedilol on PMN responses in vitro, we observed that carv edilol dose dependently modulated generation of superoxide ions by NADPH ox idase when induced by the formylpeptide formyl-methionyl-leucyl-phenylalani ne (fMLP) or the phorbol ester phorbol myristate acetate. This effect was n ot coupled to diminished phospholipase C activity. In contrast to the effec t on NADPH oxidase, neither the fMLP-elicited NO generation by PMN nor the response of the murine macrophage cell line J774 to lipopolysaccharide was affected. There was no evidence from cell-free assay systems that carvedilo l is a scavenger for superoxide ions or NO. Moreover, carvedilol did not af fect other reactions dependent on NO, e.g. spontaneous or fMLP-stimulated P MN migration or lipoxin A(4)-, fMLP-, or A23187-induced neutrophil cytotoxi city for human umbilical vein endothelial cells. Thus, these effects point to the possibility that carvedilol modulates the NADPH oxidase of PMN but l eaves the nitric oxide synthase of phagocytes intact. (C) 2000 Elsevier Sci ence Inc.