VASORELAXANT EFFECT OF THE POTASSIUM CHANNEL ACTIVATOR, RWJ-29009, ISTISSUE SELECTIVE

Potassium channel activators have potential cardioprotective propertie s, in part due to their ability to increase coronary blood flow. We co mpared the vasorelaxant properties of potassium channel activators, a calcium channel blocker (nicardipine) and a direct smooth muscle relax ant (sodium nitroprusside) in the canine coronary artery, the femoral artery and the saphenous vein precontracted with 0.03 muM endothelin-1 . In the circumflex coronary artery, RWJ 29009, a novel and potent pot assium channel activator, maximally relaxed the precontracted rings wi th 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 muM concentration. In both femoral artery and saph enous vein, all agents relaxed the precontracted rings only at much hi gher concentrations, and the relaxations were only 75% of maximal rela xation. The results show that while all vasodilators preferentially re lax the coronary artery, potassium channel activators appear to be the most selective and potent of these agents.