Calmidazolium, a calmodulin inhibitor, inhibits endothelium‐dependent relaxations resistant to nitro‐l‐arginine in the canine coronary artery

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Abstract
1 The role of calmodulin in endothelium-dependent relaxations in the canine coronary artery, was investigated by use of the inhibitor of calmodulin, calmidazolium. 2 The endothelium-dependent relaxations to adenosine diphosphate (ADP) and nebivolol, a β-adrenoceptor antagonist, in control solution, and to bradykinin in high potassium solution (to inhibit endothelium-dependent hyperpolarization), were abolished by nitro-l-arginine (30 μm), an inhibitor of nitro oxide-synthase. Calmidazolium (10 μm) did not inhibit these relaxations. 3 Calmidazolium did not affect the endothelium-independent relaxations to SIN-1, an exogenous donor of nitric oxide (NO). 4 The relaxations to bradykinin and to the calcium ionophore A23187 in control solution were inhibited to a small extent by calmidazolium (10 μm). 5 Bradykinin and A23187 induced relaxations in the presence of nitro-l-arginine (30 μm) that were abolished by calmidazolium (10 μm) but not affected by glibenclamide (10 μm), an inhibitor of ATP-sensitive K+ channels. 6 The endothelium-independent relaxations to lemakalim, an ATP-sensitive K+ channel opener, were not affected by calmidazolium (10 μm) but were inhibited by glibenclamide (10 μm). 7 These results suggest that calmidazolium does not inhibit the endothelium-dependent relaxations due to endothelium-derived NO in the canine coronary artery but inhibits either the production of endothelium-derived hyperpolarizing factor (EDHF) from endothelial cells or its effects on vascular smooth muscle cells. Furthermore these results suggest that EDHF contributes to endothelium-dependent relaxations in the canine coronary artery.