Nicorandil increases adenosine 5′-monophosphate-primed interstitial adenosine via activation of ecto-5′-nucleotidase in rat hearts

Abstract

With the use of microdialysis techniques, we examined the effects of nicorandil, a hybrid of an ATP-sensitive K⁺ (K_ATP) channel opener and a nitrate compound, on the production of interstitial adenosine in rat hearts in situ. The level of dialysate adenosine measured under a constant supply of adenosine 5′-monophosphate (AMP) reflected the activity of endogenous ecto-5′-nucleotidase. Nicorandil (0.3–3 mM) increased the level of AMP (100 μM)-primed dialysate adenosine in a concentration-dependent manner, and this effect was completely abolished by the guanylate cyclase inhibitor, methylene blue (100 μM), but not by the K_ATP channel blocker, glibenclamide (10 μM). Another K_ATP channel opener, cromakalim (0.1–1 mM), did not increase the production of AMP-primed dialysate adenosine. These results suggest that nicorandil increases the level of interstitial adenosine via cyclic guanosine monophosphate-mediated activation of ecto-5′-nucleotidase.