Vasorelaxant effect of the potassium channel activator, RWJ 29009, is tissue selective

Potassium channel activators have potential cardioprotective properties, in part due to their ability to increase coronary blood flow. We compared the vasorelaxant properties of potassium channel activators, a calcium channel blocker (nicardipine) and a direct smooth muscle relaxant (sodium nitroprusside) in the canine coronary artery, the femoral artery and the saphenous vein precontracted with 0.03 microM endothelin-1. In the circumflex coronary artery, RWJ 29009, a novel and potent potassium channel activator, maximally relaxed the precontracted rings with an EC50 of 1.9 nM. Cromakalim (EC50 = 220 nM) and nitroprusside (EC50 = 109 nM) were also active. Nicardipine (EC50 = 16.6 nM) produced only a 70% relaxation at 1 microM concentration. In both femoral artery and saphenous vein, all agents relaxed the precontracted rings only at much higher concentrations, and the relaxations were only 75% of maximal relaxation. The results show that while all vasodilators preferentially relax the coronary artery, potassium channel activators appear to be the most selective and potent of these agents.