Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway

We investigated the effects of nicorandil, which is a hybrid between a nitr ate and an ATP-sensitive potassium channel (K-ATP) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 muM to 1 mM inhibited [H-3]thym idine incorporation into rat mesangial cells in a concentration-dependent m anner. Nicorandil (1 muM to 1 mM) also inhibited the number of cells. Nicor andil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminate d the inhibition of mesangial cell proliferation by nicorandil. Methylene b lue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicora ndil on mesangial cell proliferation. We also examined the effects of KATP mediators. Cromakalim, a KATP activator, and glibenclamide, a KATP inhibito r, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell prolif eration are mediated via the protein kinase G pathway. Copyright (C) 2001 S . Karger AG, Basel.