Inhibitory Effects of Nicorandil on Rat Mesangial Cell Proliferation via the Protein Kinase G Pathway

Publisher: Karger

E-ISSN: 2235-3186|87|3|263-268

ISSN: 1660-8151

Source: Nephron, Vol.87, Iss.3, 2001-03, pp. : 263-268

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Abstract

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (KATP) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 µM to 1 mM inhibited [3H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 µM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3′,5′-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of KATP mediators. Cromakalim, a KATP activator, and glibenclamide, a KATP inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.