Effects of exercise training and hypercholesterolemia on adenosine activation of voltage-dependent K+ channels in coronary arterioles
Effects of exercise training and hypercholesterolemia on adenosine activation of voltage-dependent K+ channels in coronary arterioles
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DOI：
10.1152/japplphysiol.90958.2008
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发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Bowles, Douglas K.
中科院分区：
文献类型：
--
作者：
Heaps, Cristine L.;Jeffery, Elise C.;Bowles, Douglas K.
Heaps CL，Jeffery EC，Laine GA，Price EM，Bowles DK.运动训练和高胆固醇血症对腺苷激活冠状小动脉电压依赖性K（+）通道的影响J Appl Physiol 105：1761-1771，2008.首次发表于2008年10月2日; doi：10.1152/japplphysiol.90958.2008。高胆固醇血症猪的冠状小动脉显示腺苷介导的血管舒张减弱，这归因于电压依赖性K（+）（Kv）通道刺激的消除。在本研究中，我们测试的假设，运动训练将纠正受损的腺苷诱导的扩张冠状动脉从高胆固醇血症猪通过恢复腺苷激活KV通道和血管扩张的受体非依赖性腺苷酸环化酶激活剂，毛喉素，也将在高胆固醇血症猪的小动脉衰减。将猪随机分配到对照组（NC）或高脂肪、高胆固醇（HC）饮食组，持续20周。饮食开始后四周，将来自两组的猪分配到运动训练（Ex; 5天/周，持续16周）或久坐（Sed）方案，产生四组猪：NC-Sed、NC-Ex、HC-Sed和HC-Ex。与NC对应物相比，HC-Sed和HC-Ex猪的小动脉（类似于150 μ m）显示腺苷介导的扩张受损，这归因于消除4-氨基吡啶（4-AP; 1 mM）敏感的Kv通道激活。小动脉平滑肌全细胞Kv电流显着降低HC-Sed与NC-Sed相比，虽然HC-Ex和NC-Ex没有差异。毛喉素介导的扩张减弱4-AP（1 mM），并在浓度依赖性的方式由四乙基铵（TEA; 0.1-1 mM）在NC-Sed，但不是HC-Sed。此外，TEA敏感的Kv电流减少，在细胞的HC-Sed相比，NC-Sed猪。定量RT-PCR显示NC-Sed和HC-Sed猪的小动脉中Kv3.1和3.3的表达水平相似，Kv1.1、3.2和3.4的表达不可检测。综上所述，这些结果表明，高胆固醇血症介导的腺苷诱导的冠状动脉血管舒张的衰减不能通过运动训练来纠正，并且可能归因于腺苷酸环化酶与高度TEA敏感的Kv通道亚型偶联途径的损伤。
Heaps CL, Jeffery EC, Laine GA, Price EM, Bowles DK. Effects of exercise training and hypercholesterolemia on adenosine activation of voltage-dependent K(+) channels in coronary arterioles. J Appl Physiol 105: 1761-1771, 2008. First published October 2, 2008; doi:10.1152/japplphysiol.90958.2008.-Coronary arterioles from hypercholesterolemic swine display attenuated adenosine-mediated vasodilatation that is attributable to the elimination of voltage-dependent K(+) (Kv) channel stimulation. For the present study, we tested the hypotheses that exercise training would correct impaired adenosine-induced dilatation in coronary arterioles from hypercholesterolemic pigs through restoration of adenosine activation of Kv channels and that vasodilatation to the receptor-independent adenylyl cyclase activator, forskolin, would also be attenuated in arterioles from hypercholesterolemic pigs. Pigs were randomly assigned to a control (NC) or high-fat, high-cholesterol (HC) diet for 20 wk. Four weeks after the diet was initiated, pigs from both groups were assigned to exercise training (Ex; 5 days/wk for 16 wk) or sedentary (Sed) protocols, resulting in four groups of pigs: NC-Sed, NC-Ex, HC-Sed, and HC-Ex. Arterioles (similar to 150 mu m) from both HC-Sed and HC-Ex pigs displayed impaired adenosine-mediated dilatation that was attributable to the elimination of 4-aminopyridine (4-AP; 1 mM)-sensitive Kv channel activation compared with NC counterparts. Arteriolar smooth muscle whole cell Kv currents were significantly reduced in HC-Sed compared with NC-Sed, although HC-Ex and NC-Ex did not differ. Forskolin-mediated dilatation was attenuated by 4-AP (1 mM) and in a concentration-dependent manner by tetraethylammonium (TEA; 0.1-1 mM) in NC-Sed but not HC-Sed. Further, TEA-sensitive Kv currents were diminished in cells of HC-Sed compared with NC-Sed pigs. Quantitative RT-PCR revealed similar expression levels of Kv3.1 and 3.3 in arterioles of NC-Sed and HC-Sed swine with undetectable expression of Kv1.1, 3.2, and 3.4. Taken together, these results suggest that hypercholesterolemia-mediated attenuation of adenosine-induced vasodilatation in coronary arterioles is not corrected by exercise training and is likely attributable to an impairment in the pathway coupling adenylyl cyclase with a highly TEA-sensitive Kv channel isoform(s).