NITROVASODILATORS HAVE PROLIFERATIVE AS WELL AS ANTIPROLIFERATIVE EFFECTS

The nitrovasodilator sodium nitroprusside (SNP) is mitogenic in rabbit dermal fibroblasts within the concentration range of 0.1-100-mu-M. In contrast, SNP at > 100-mu-M is antiproliferative and at concentrations > 250-mu-M is cytotoxic in fibroblasts. SNP (5-1,000-mu-M) is mitogenic in porcine and rabbit aortic smooth muscle cells but is antiproliferative at concentrations > 1,000-mu-M. A prolonged incubation period (24 h) with SNP is necessary to observe mitogenic effects and the effects of SNP on smooth muscle cells occur at near-maximal stimulation of the soluble guanylate cyclase. These data demonstrate that SNP has both mitogenic and antiproliferative effects in fibroblasts and smooth muscle cells and that the mitogenic effect may be related to stimulation by nitric oxide of the soluble guanylate cyclase.