CPA induces a sustained increase in [Ca²⁺](i) of endothelial cells in situ and relaxes porcine coronary artery

Using fura 2 fluorometry, we investigated the effect of cyclopiazonic acid (CPA), an inhibitor of Ca²⁺ pump adenosinetriphosphatase of the endoplasmic reticulum, on cytosolic Ca²⁺ concentration ([Ca²⁺ ](i)) and tension in porcine aortic valvular endothelial cells and coronary arterial strips with endothelium. In normal physiological salt solution, CPA induced a sustained increase in [Ca²⁺](i) in the valvular strips, whereas in Ca²⁺- free physiological salt solution, CPA elicited a transient elevation of [Ca²⁺](i). CPA (30 μM) relaxed coronary strips with endothelium precontracted by 100 nM U-46619; this relaxation was partially inhibited by N(ω)-nitro-L-arginine (100 μM). These results indicate that the CPA- induced increase in [Ca²⁺](i) depends on the Ca²⁺ release and the Ca²⁺ influx in the endothelial cells in situ and that the CPA-induced endothelium- dependent decreases in [Ca²⁺](i) and tension in the smooth muscle are due to the combined effect of N(ω)-nitro-L-arginine-sensitive and -resistant factors.