Low-density lipoprotein-induced formation of nitric oxide by cultured vascular smooth muscle cells of the rat.

Abstract

There is evidence that low-density lipoprotein (LDL) plays a crucial role in atherogenesis. On the cellular level, LDL has been shown to activate a number of mechanisms involved in atherogenesis and vasoconstriction. Local immoderate vasoconstriction is physiologically antagonized by nitric oxide, which is released from the endothelium. To find out whether LDL also influences the synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of arginine to citrulline and the production of nitrite were determined as a measure of nitric oxide formation. After incubation of rat vascular smooth muscle cells with native LDL (25 micrograms mL-1) for 24 h, the production of both L-[14C]-citrulline [39600 (3600) cpm mg-1 cell protein] and nitric oxide [2.95 (0.56) mumol L-1] were about twice and 1.5-fold the amount of the corresponding values in untreated cells (mean +/- SD, P < 0.05, n = 4). Oxidized LDL was less effective than the native form. The presence of the arginine analogue NG-methyl-L-arginine reduced citrulline production dose-dependently but augmented DNA synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6-fold increase in cyclic GMP production following a 24-h incubation [control = 10.9 (3.8) pmol mg-1 cell protein, P = 0.016]. The results suggest that native LDL might partly impair its atherogenic potential on the vasculature by stimulating the production by smooth muscle cells of both nitric oxide and cyclic GMP.