Enhanced phenylephrine-induced rhythmic activity in the atherosclerotic mouse aorta via an increase in opening of KCa channels:: relation to Kv channels and nitric oxide

被引:22
作者
Jiang, JH
Thorén, P
Caligiuri, G
Hansson, GK
Pernow, J [1 ]
机构
[1] Karolinska Hosp, Dept Med, Div Cardiol, S-17176 Stockholm, Sweden
[2] Karolinska Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden
[3] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden
关键词
apolipoprotein E; endothelium; mouse; aorta; nitric oxide; potassium channels; calcium channels;
D O I
10.1038/sj.bjp.0702855
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E-o x LDLRo) develop atherosclerosis. The aim of this study was to investigate changes in endothelium-dependent vasodilation and vasomotion in thoracic aortic rings of E-o x LILRo mice. 2 K+-induced contractions of the aorta from E-o x LDLRo mice were stronger than those from control mice. The sensitivity of E-o x LDLRo aorta to phenylephrine (PE) was decreased but the maximal contractions were increased. Acetylcholine-induced, but not sodium nitroprusside-induced, relaxations of E-o x LDLRo aorta was decreased. 3 PE induced rhythmic activity in both E-o x LDLRo and control aorta but the amplitude was larger in E-o x LDLRo than in control mice. PE-induced rhythmic activity in both E-o x LDLRo and control aorta was augmented by increase in extracellular Ca2+-concentration, but was abolished by removal of the endothelium, the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine methyl ester, the guanylate cyclase inhibitor LY-83583, high K+ solution and ryanodine. 4 4-Aminopyridine, a voltage-dependent potassium (K-v) channel blocker, increased basal tension and induced rhythmic activity in E-o x LDLRo aorta but not in control aorta. 5 The Ca2+-activated potassium (K-ca) channel blockers tetraethylammonium and charybdotoxin abolished PE-induced rhythmic activity in E-o x LDLRo aorta. 6 In conclusion, opening of K-v channels in E-o x LDLRo mice aorta is reduced and it is susceptible to be depolarized resulting in Ca2+ entry. The vascular smooth muscle is then dependent on compensatory mechanisms to limit Ca2+-entry. Such mechanisms may be decreased sensitivity to vasoconstrictors, or increased opening of K-ca channels by NO via a cyclic GMP-dependent mechanism.
引用
收藏
页码:637 / 646
页数:10
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