Effects of the potassium channel openers KRN4884 and levcromakalim on the contraction of rat aorta induced by A23187, compared with nifedipine.

We examined the different vasodilatory effects of the K+ channel openers levcromakalim and 5-amino-N- [2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine (KRN4884), and the Ca2+ channel blocker nifedipine in the rat aorta. KRN 4884 (10(-10)-10(-5) M) and nifedipine (10(-10)-10(-5) M) produced concentration-dependent relaxation in the rat aorta precontracted by 25 mM KCl. The K+ channel blocker glibenclamide (1 microM) inhibited the relaxation induced by KRN4884 but did not influence nifedipine-induced relaxation. KRN4884 had almost no effect on contraction induced by 80 mM KCl, whereas nifedipine completely relaxed the muscle precontracted by 80 mM KCl, whereas nifedipine completely relaxed the muscle precontracted by 80 mM KCl. These results indicate that KRN4884 is a K+ channel opener. We investigated the relaxant effects of KRN4884 (10(-10)-10(-5) M), levcromakalim (10(-9)-10(-5) M) and nifedipine (10(-9)-10(-5) M) on A23187 (1 microM)-induced contraction. KRN4884 and levcromakalim had a potent relaxant effect but nifedipine only a weak effect on the smooth muscle contracted by A23187. Glibenclamide (1 microM) inhibited the relaxation induced by KRN4884 and levcromakalim, but did not influence the nifedipine-induced relaxation. KRN4884 (1 microM) produced a larger relaxation of A23187-induced contraction but had little effect on the increase in intracellular [Ca2+] induced by A23187. These results suggest that KRN4884 is a specific K+ channel opener and its vasodilating mechanisms involve not only deactivation of Ca2+ channels but also a decrease in the Ca2+ sensitivity of contractile elements.