Prasad A, Husain S, Schenke W, Mincemoyer R, Epstein N, Quyyumi A A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
J Am Coll Cardiol. 2000 Nov 1;36(5):1467-73. doi: 10.1016/s0735-1097(00)00892-5.
The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors.
Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone.
In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 microg/min) and BK (62.5 ng/min and 4 microg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed.
There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype.
Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype.
我们研究的目的是调查动脉粥样硬化患者或其危险因素患者的冠状动脉激肽受体功能。
尽管乙酰胆碱（ACH）被用作体内测试血管功能的探针，但内源性缓激肽（BK）调节静息和血流介导的心外膜张力。
在53例轻度动脉粥样硬化或其危险因素患者和9例对照受试者中，通过冠状动脉内注射ACH（30微克/分钟）和BK（62.5纳克/分钟和4微克/分钟）测试内皮依赖性血管运动，并用硝普钠测试非内皮依赖性功能。在心脏起搏期间评估代谢性血管舒张（n = 19）。进行了与血清血管紧张素转换酶（ACE）水平和ACE插入/缺失基因型的相关性分析。
随着危险因素数量的增加，ACH介导的微血管舒张逐渐受损（p = 0.025，方差分析）。相比之下，BK和硝普钠介导的微血管舒张在所有组中相似。同样，心外膜冠状动脉对ACH和BK的反应之间没有相关性；对ACH收缩或舒张的节段对BK有相似的舒张反应。缓激肽介导的血管运动，而不是ACH介导的血管运动，在起搏时收缩的心外膜节段中受到抑制。最后，高ACE水平患者和ACE DD基因型患者的心外膜BK反应受到抑制。
动脉粥样硬化中的内皮功能障碍似乎是受体特异性的，涉及毒蕈碱受体，而激肽受体途径相对保留。生理应激期间心外膜冠状动脉的异常反应性由BK而不是ACH反应更好地体现。缓激肽活性以及因此的生理性冠状动脉血管运动似乎受血清ACE水平和ACE插入/缺失基因型的影响。
