Iloprost dilates rat small arteries: Role of K-ATP- and K-Ca-channel activation by cAMP-dependent protein kinase

被引:78
作者
Schubert, R [1 ]
Serebryakov, VN [1 ]
Mewes, H [1 ]
Hopp, HH [1 ]
机构
[1] RUSSIAN ACAD MED SCI, CARDIOL RES CTR, INST EXPT CARDIOL, MOSCOW 121552, RUSSIA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1997年 / 272卷 / 03期
关键词
vasodilation; potassium channel; smooth muscle;
D O I
10.1152/ajpheart.1997.272.3.H1147
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effect of the stable prostacyclin analog iloprost and its mechanism of action were investigated with the use of pressurized rat tail small arteries with a spontaneous myogenic tone. Iloprost concentration dependently dilated these vessels with a half-maximal effective dose of 5.0 +/- 0.5 x 10(-8) M. Application of 10(-7)-10(-6) M glibenclamide, a blocker of ATP-sensitive potassium (K-ATP) channels, inhibited the iloprost-induced dilation. Glibenclamide did not affect the basal vessel diameter. The application of 5 x 10(-5)-10(-3) M tetraethylammonium (TEA) and 5 x 10(-9)-10(-7) M iberiotoxin, blockers of calcium-activated potassium (Kc,) channels, decreased vessel diameter in the presence of iloprost. Both TEA and iberiotoxin reduced the basal vessel diameter. Glibenclamide at 10(-6) M inhibited the dilation produced by 5 x 10(-5) M Sp-5,6-DCl-cBIMPS, an activator of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. Iberiotoxin at 10(-7) M decreased vessel diameter in the presence of Sp-5,6-DCl-cBIMPS. H-89 and Rp-8-CPT-cAMPS, blockers of cAMP-dependent protein kinase A (PKA), inhibited the iloprost-induced dilation of these vessels. With use of the whole cell configuration of the patch-clamp technique, it was observed that 5 x 10(-7) M iloprost enhanced an outward current, determined largely by Kc, channels, 1.79 +/- 0.17-fold in freshly isolated smooth muscle cells from rat tail small artery. These data show that iloprost dilates rat tail small arteries with a spontaneous myogenic tone and suggest that K-ATP as well as Kc, channels are involved in this effect, which is mediated, at least partly, by PKA.
引用
收藏
页码:H1147 / H1156
页数:10
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    WEIR, B
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    COOK, D
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