Enhanced antiproliferative effect of nitric oxide in cultured smooth muscle cells from diabetic rats

We examined the influence of experimental diabetes on the proliferation of cultured vascular smooth muscle cells (VSMCs) in presence of a nitric oxide (NO)-generating agent, sodium nitroprusside (SNP), and 8-bromo-cGMP. VSMC cultures were prepared from aortas of control and streptozotocin-diabetic rats. SNP induced a time- and dose-dependent inhibition of control and diabetic VSMC proliferation, consistent with the data on [H-3]thymidine incorporation, cell counts, and index of culture mass. However, the responses to SNP were significantly enhanced in VSMCs from diabetic rats. SNP induced an increased dose-dependent accumulation of intracellular cGMP in diabetic VSMCs. In contrast, growth-inhibitory responses to 8-bromo-cGMP were not significantly different between the two VSMC models. Moreover, basal cGMP content in VSMCs was lower in diabetic rats than in controls, a result that can explain the enhanced proliferation observed in VSMCs from diabetic rats. These results suggest an enhanced antiproliferative effect of NO in VSMCs from diabetic rats through increased cGMP production. Therefore, experimental diabetes may impair and up-regulate soluble guanylate cyclase activity in VSMCs.