Regulation of growth of cultured smooth muscle cells from diabetic rats by interleukin-1 beta: Role of nitric oxide

We examined the influence of streptozotocin-induced diabetes on the growth of cultured rat aortic smooth muscle cells in the presence of interleukin-1 beta. Interleukin-1 beta induced a dose-dependent biphasic effect on proliferation of diabetic and control smooth muscle cells, consistent with the data on [H-3]thymidine incorporation and cell counts. However, the major effect of interleukin-1 beta was to stimulate growth of diabetic cells and inhibit growth of control cells. Furthermore, interleukin-1 beta induced a dose-dependent increase in nitric oxide (NO) release and in intracellular cyclic GMP accumulation: nitrite release was similar in both smooth muscle cell models but cyclic GMP accumulation was greater in diabetic cells than in controls. These results suggest that the inhibitory loop involving NO is not effective enough to completely counterbalance the stimulatory effects of interleukin-1 beta on diabetic cells. Therefore, experimental diabetes may modify the interleukin-1 beta-regulated smooth muscle cell growth.