Inhibitory properties of NIP-121, a potassium channel opener, on high potassium- and norepinephrine-induced contraction and calcium mobilization in rat aorta.
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.
Yamashita
T
T
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Saitama, Japan.
Masuda
Y
Y
Tanaka
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; D014665:Vasodilator Agents; C070366:NIP 121; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine