Matsuda T, Okazaki K, Kato Y, Tanaka H, Shigenobu K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
J Cardiovasc Pharmacol. 1995 Oct;26(4):608-13. doi: 10.1097/00005344-199510000-00016.
Myocardial effects of NIP-121, a novel compound with potent vasorelaxant activity, were examined in comparison with those of cromakalim in isolated tissue and cells from guinea pig hearts. NIP-121 and cromakalim concentration-dependently reduced the action potential duration (APD) of isolated papillary muscle; the effect was antagonized by glibenclamide. In isolated ventricular tissue, NIP-121 and cromakalim decreased the contractile force concentration dependently. In these two experiments, the potency of NIP-121 was approximately 20 times higher than that of cromakalim. The effects of NIP-121 and cromakalim on membrane currents were examined in voltage-clamped ventricular myocytes. NIP-121 (10(-6) M) and cromakalim (3 x 10(-5) M) increased the steady-state outward currents. The normal inwardly rectifying current-voltage relationship changed to a linear relationship that reversed at the K+ current reversal potential. The current activated by NIP-121 and cromakalim was inhibited either by glibenclamide or by increased intracellular ATP concentration. NIP-121, at this concentration, had little effect on the calcium current. Thus, NIP-121 was demonstrated to produce AP shortening and decrease in contractile force through activation of ATP-sensitive K+ currents in cardiac muscle, with a potency approximately 20 times higher than that of cromakalim.
