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 F2α, 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 10−5M increased the activity of (Ca2+ + Mg2+)-ATPase significantly at a free calcium concentration of 0.3 μM. At 10−6M, 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.