Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome.
Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome.
复制标题
DOI：
10.3181/0812-rm-350
复制
发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Laughlin MH
中科院分区：
文献类型：
--
作者：
Bender SB;Tune JD;Borbouse L;Long X;Sturek M;Laughlin MH
联合代谢综合征(METS)的发病是一个复杂的进行性过程，涉及多种心血管危险因素。虽然已建立甲硫氨酸的患者表现出冠状动脉血流储备减少，并且甲硫氨酸的个别成分减少微血管扩张，但关于早期甲硫氨酸对冠脉血流控制机制的影响知之甚少。因此，我们验证了这一假说，即早期METS患者的冠状动脉对腺苷的扩张是通过A2受体功能降低和K+通道参与减少而减弱的。分别饲喂对照组或高脂高脂饲料9周，以诱发早期蛋氨酸蛋氨酸日粮。血管内超声活体检测冠状动脉粥样斑块。采用冠脉内注射腺苷的方法测定冠脉内扩张。此外，分离、插管和加压至60cmH2O，以进行腺苷扩张的体外药理学评估。冠状动脉粥样硬化在不同组之间没有差异，表明METS处于早期阶段。两组间冠状动脉对腺苷(体内)和2-氯腺苷(2-CAD；体外)的扩张相似。在对照小动脉中，2-CAD介导的扩张仅通过选择性A2A受体抑制而减少，而在蛋氨酸小动脉中只有A2A/2B双重抑制才减少这一反应。甲硫氨酸可降低小动脉A2B受体蛋白的表达，但不能降低A2A受体蛋白的表达。阻断电压依赖性K+(Kv)通道降低了两组小动脉对2-CAD的敏感性，而ATP敏感性K+(KATP)通道的抑制仅降低了对照小动脉的敏感性。我们的数据表明，在冠状动脉血管扩张剂储备明显减少之前，介导冠状动脉小动脉扩张至腺苷的机制在早期甲胎蛋白综合征患者中发生了改变。
Onset of the combined metabolic syndrome (MetS) is a complex progressive process involving numerous cardiovascular risk factors. Although patients with established MetS exhibit reduced coronary flow reserve and individual components of the MetS reduce microvascular vasodilation, little is known concerning the impact of early-stage MetS on the mechanisms of coronary flow control. Therefore, we tested the hypothesis that coronary arteriolar dilation to adenosine is attenuated in early-stage MetS by reduced A2 receptor function and diminished K+ channel involvement. Pigs were fed control or high-fat/cholesterol diet for 9 weeks to induce early-stage MetS. Coronary atheroma was determined in vivo with intravascular ultrasound. In vivo coronary dilation was determined by intracoronary adenosine infusion. Further, apical coronary arterioles were isolated, cannulated and pressurized to 60 cmH2O for in vitro pharmacologic assessment of adenosine dilation. Coronary atheroma was not different between groups, indicating early-stage MetS. Coronary arteriolar dilation to adenosine (in vivo) and 2-chloroadenosine (2-CAD; in vitro) was similar between groups. In control arterioles, 2-CAD-mediated dilation was reduced only by selective A2A receptor inhibition, whereas only dual A2A/2B inhibition reduced this response in MetS arterioles. Arteriolar A2B, but not A2A, receptor protein expression was reduced by MetS. Blockade of voltage-dependent K+ (Kv) channels reduced arteriolar sensitivity to 2-CAD in both groups, whereas ATP-sensitive K+ (KATP) channel inhibition reduced sensitivity only in control arterioles. Our data indicate that the mechanisms mediating coronary arteriolar dilation to adenosine are altered in early-stage MetS prior to overt decrements in coronary vasodilator reserve.