Increased tissue angiotensin-converting enzyme activity impairs bradykinin-induced dilation of coronary arterioles in obesity.
Increased tissue angiotensin-converting enzyme activity impairs bradykinin-induced dilation of coronary arterioles in obesity.
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DOI：
10.1253/circj.cj-12-1163
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Bagi Z
中科院分区：
文献类型：
--
作者：
Feher A;Cassuto J;Szabo A;Patel V;Vinayak Kamath M;Bagi Z
缓激肽（BK）是调节冠状动脉血流的关键介质。它被血管紧张素转换酶（ACE）降解，但目前尚不清楚的是，组织ACE活性增强是否会干扰BK诱导的肥胖症冠状动脉血管舒张。从正常或高脂饮食（HFD）大鼠和接受心脏手术的瘦型或肥胖型患者（n=74）中分离冠状小动脉（~100 μm）。我们发现，BK诱导的扩张HFD大鼠的冠状动脉减少，与对照组相比。当在体外给药时，血管紧张素转换酶抑制剂，卡托普利，恢复冠状动脉扩张反应BK在HFD大鼠，但不影响控制反应。在冠状动脉内皮中检测到丰富的ACE表达，这与HFD小动脉中ACE活性增加相关，通过对ACE底物血管紧张素I的反应增加来测量。此外，我们发现，在肥胖患者的冠状小动脉，BK诱导的扩张增强了体外卡托普利管理。相应地，与非肥胖患者相比，肥胖患者的冠状动脉ACE活性增加。Logistic回归分析显示，肥胖患者手术前服用ACE抑制剂表现出增强的扩张反应BK。我们证明了增强组织ACE活性的肥胖受试者的冠状动脉，这导致冠状动脉扩张反应降低BK。我们提供了一个理由ACE抑制剂治疗肥胖患者，以改善冠状动脉微血管扩张。
Bradykinin (BK) is a key mediator regulating coronary blood flow. It is degraded by angiotensin-converting enzyme (ACE), but what is unknown is whether enhanced tissue ACE activity interferes with BK-induced coronary vasodilation in obesity. Coronary arterioles (~100 μm) were isolated from rats on a normal or high-fat diet (HFD) and from lean or obese patients undergoing heart surgery (n=74). We found that BK-induced dilation was diminished in the coronary arterioles of HFD rats, when compared with controls. When administered in vitro, the ACE inhibitor, captopril, restored the coronary dilation response to BK in HFD rats, but did not affect control responses. Abundant ACE expression was detected in coronary endothelium, which was associated with increased ACE activity in HFD arterioles, as measured by increased response to the ACE substrate, angiotensin I. Moreover, we found that in the coronary arterioles of obese patients, BK-induced dilation was augmented by in vitro captopril administration. Correspondingly, ACE activity was increased in the coronary arterioles of obese patients when compared with the non-obese. Logistic regression analysis revealed that obese patients taking ACE inhibitors prior to surgery exhibited an enhanced dilation response to BK. We demonstrated augmented tissue ACE activity in the coronary arterioles of obese subjects, which leads to reduced coronary dilation response to BK. We provide a rationale for ACE inhibitor therapy in obese patients to improve dilatation of coronary microvessels.
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