DIFFERENTIAL VASODILATOR PROPERTIES OF KRN2391, CROMAKALIM, NITROGLYCERIN AND NIFEDIPINE IN RABBIT ISOLATED FEMORAL-ARTERY AND VEIN

1 The selectivity for artery and vein of KRN2391, cromakalim, nitrogly cerin and nifedipine was examined in isolated femoral artery and vein preparations of the rabbit. 2 All drugs produced a concentration-depen dent relaxation in both femoral artery and vein. 3 Nitroglycerin was m ore potent in femoral vein than in femoral artery at all concentration s. The EC(50) value obtained in the vein was about 14 times smaller th an that obtained in artery. 4 Cromakalim and nifedipine were almost eq uipotent on both vascular preparations. Cromakalim at the highest conc entration (10(-5)M) produced 88 and 78% relaxation in femoral artery a nd vein, respectively. The maximum relaxation induced by nifedipine (1 0(-6)M) was less than 50% in both preparations. 5 KRN2391 was active a t a lower concentration in the vein than in the artery and its maximum relaxation at 10(-5)M was about 90% in both preparations. 6 Glibencla mide (10(-6)M) inhibited the vasorelaxation caused by KRN2391 in both artery and vein. Methylene blue (10(-5)M) also inhibited the relaxant action of KRN2391 but this action was slight in the artery. 7 These re sults suggest that KRN2391 and nitroglycerin are more potent in the ve in than in the artery and cromakalim and nifedipine are equipotent in both. It is considered that the relaxation induced by low concentratio ns of KRN2391 reflects predominantly its action as a nitrate and that at high concentrations it acts as a K+ channel opener in addition to i ts nitrate action. The different vascular selectivities of these drugs are thought to relate to the differences in their mechanisms of actio n in vascular smooth muscle.