| Abstract: | We examined the effects of NIP-121, a potassium channel opener, on KCl- and norepinephrine (NE)-induced contraction, the phasic-contraction under the Ca(2+)-free condition and cytosolic free-Ca2+ mobilization using isolated rat aorta. NIP-121 as well as cromakalim inhibited, in the KCl- and NE-contractions concentration dependently. Glibenclamide, an ATP-sensitive potassium channel blocker, competitively reversed their inhibition. On the other hand, they did not inhibit the phasic-contractions induced by NE in Ca(2+)-free medium. In Fura-2-loaded rat aorta, NIP-121 inhibited only the late phase of the NE-induced cytosolic Ca2+ level ([Ca2+]cyt) increases that were inhibited by nicardipine. However, it did not inhibit the first [Ca2+]cyt increase, which was completely abolished by repeated applications of NE in Ca(2+)-free medium. Neither did it inhibit phorbol ester-induced contraction. The vasorelaxant mechanism of NIP-121 is attributable to the decrease in Ca2+ influx passing through the membrane Ca2+ permeable systems. In addition, inhibition of Ca2+ release from sarcoplasmic reticulum (SR) and of protein kinase C (PKC) activation may not be involved in vasorelaxation induced by NIP-121. |
