Effect of nicorandil on the cytosolic free calcium concentration and microsomal (Ca2+ + Mg2+)-ATPase activity of vascular smooth muscle cells

Abstract

The influence of nicorandil, a potent antianginal drug, on cellular calcium in vascular smooth muscle cells (VSMC) was investigated by studying its effects on the cytosolic free calcium concentration ([Ca2+]i) and calcium-stimulated magnesium-dependent ATPase [(Ca2+ + Mg2+)-ATPase] in the cells. VSMC were prepared from rat aorta, and their [Ca2+]i level was determined by measuring the fluorescence of the free calcium indicator, fura 2. Preincubation with nicorandil for 5 min significantly decreased the rise in [Ca2+]i evoked by addition of either angiotensin II in control solution or prostaglandin F2 alpha, the latter in either the presence or absence of extracellular calcium. The effect of nicorandil on (Ca2+ + Mg2+)-ATPase activity in the microsomal fraction of porcine coronary artery smooth muscle, which is rich in plasma membranes and sarcoplasmic reticulum, was also investigated. Nicorandil at concentrations of 10(-6) and 10(-5) M increased the activity of (Ca2+ + Mg2+)-ATPase significantly at a free calcium concentration of 0.3 microM. At 10(-6) M, nicorandil significantly decreased the Kd for calcium of this enzyme without significantly changing its Vmax. These data suggest that nicorandil suppressed increase of [Ca2+]i, possibly by stimulating (Ca2+ + Mg2+)-ATPase, thereby inhibiting contraction of vascular smooth muscle.