Nicorandil-Induced Vasodilation : K+ Conductance-Dependent and -Independent Actions
Hosner, Jack McLean
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The vasodilating effects of nicorandil on norepinephrine-induced contraction were studied in both rabbit mesenteric and thoracic aortic arteries using tissue baths and a polygraph. Pretreatments with varying concentrations of potassium channel blockers (BaCl2, U-37,883A, and TEA) allowed for the study and comparison of nicorandil's potassium dependency in either tissue. Increasing doses of nicorandil were added to each tissue, and two distinct mechanistic components of nicorandil's actions were identified. Results indicated that a K+ conductance-dependent action predominates in rabbit mesenteric artery and a K+ conductance-independent mechanism of action predominates in rabbit aorta, although both mechanisms of action occur to some degree in both tissues. It was suggested that the former involves hyperpolarization of the cell membrane, and the latter operates by increasing intracellular cyclic GMP content.