TY - JOUR
T1 - K+ Channel-opening action and KRN2391-induced reduction of Ca2+ sensitivity of arterial smooth muscle
AU - Okada, Y.
AU - Yanagisawa, T.
AU - Yamagishi, T.
AU - Taira, N.
PY - 1993
Y1 - 1993
N2 - To clarify the vasodilating mechanism of KRN2391, a novel vasodilator having a combined nitrate-like and K+ channel-opening action, we investigated its effects on membrane potentials, intracellular Ca2+ concentrations ([Ca2+](i)) and force of contraction in canine coronary artery. KRN2391 hyperpolarized the membrane of arterial smooth muscle cells in 5 and 30 mM KCl-physiological salt solutions. KRN2391 reduced the increases in [Ca2+](i) and force of contraction induced by 30 mM KCl- physiological salt solution and the effect on [Ca2+](i) was almost abolished by 10-5 M glibenclamide, although the effect on force of contraction was only partially inhibited. The [Ca2+](i)-force curves in the presence of KRN2391 or the selective K+ channel openers Ki4032 and cromakalim were shifted to the right, as compared to the control curve determined by varying the extracellular Ca2+ concentration ([Ca2+](o)). This finding indicates that these substances reduce the Ca2+ sensitivity of contractile elements (Ca2+ desensitization). The Ca2+-desensitizing action of KRN2391 was partly antagonized by 10-5 M glibenclamide. There was no interaction between nitroglycerin and cromakalim or Ki4032. These results suggest that, in addition to the nitrate-like action, the opening of the K+ channel by KRN2391 reduces not only [Ca2+](i) but also the Ca2+ sensitivity of contractile elements, resulting in vasodilatation.
AB - To clarify the vasodilating mechanism of KRN2391, a novel vasodilator having a combined nitrate-like and K+ channel-opening action, we investigated its effects on membrane potentials, intracellular Ca2+ concentrations ([Ca2+](i)) and force of contraction in canine coronary artery. KRN2391 hyperpolarized the membrane of arterial smooth muscle cells in 5 and 30 mM KCl-physiological salt solutions. KRN2391 reduced the increases in [Ca2+](i) and force of contraction induced by 30 mM KCl- physiological salt solution and the effect on [Ca2+](i) was almost abolished by 10-5 M glibenclamide, although the effect on force of contraction was only partially inhibited. The [Ca2+](i)-force curves in the presence of KRN2391 or the selective K+ channel openers Ki4032 and cromakalim were shifted to the right, as compared to the control curve determined by varying the extracellular Ca2+ concentration ([Ca2+](o)). This finding indicates that these substances reduce the Ca2+ sensitivity of contractile elements (Ca2+ desensitization). The Ca2+-desensitizing action of KRN2391 was partly antagonized by 10-5 M glibenclamide. There was no interaction between nitroglycerin and cromakalim or Ki4032. These results suggest that, in addition to the nitrate-like action, the opening of the K+ channel by KRN2391 reduces not only [Ca2+](i) but also the Ca2+ sensitivity of contractile elements, resulting in vasodilatation.
UR - http://www.scopus.com/inward/record.url?scp=0027858318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027858318&partnerID=8YFLogxK
M3 - Article
C2 - 8185411
AN - SCOPUS:0027858318
VL - 326
SP - 33
EP - 51
JO - Archives Internationales de Pharmacodynamie et de Therapie
JF - Archives Internationales de Pharmacodynamie et de Therapie
SN - 0003-9780
ER -