Selective Attenuation of Endothelium-Mediated Vasodilation in Atherosclerotic Human Coronary Arteries
This study was undertaken to determine whether atherosclerosis impairs relaxations mediated by endothelium-derived relaxing factor (EDRF) in human coronary arteries. Epicardial coronary arteries were obtained from the hearts of cardiac transplantation patients with or without histologically document...
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Veröffentlicht in: | Circulation research 1988-02, Vol.62 (2), p.185-190 |
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Zusammenfassung: | This study was undertaken to determine whether atherosclerosis impairs relaxations mediated by endothelium-derived relaxing factor (EDRF) in human coronary arteries. Epicardial coronary arteries were obtained from the hearts of cardiac transplantation patients with or without histologically documented coronary atherosclerosis (atherosclerotic arteries were from patients aged 42–55 years, nonatherosclerotic arteries were from patients aged 14–24 years). Transverse strip preparations were mounted in organ baths for isometric tension recording. Tension was induced with prostaglandins F2a. Indomethacin (10 M) was present to prevent possible interference from endogenously formed prostaglandins. The EDRF-mediated relaxations in response to substance P (10 to 10 M), bradykinin (10 to 10 M), and Ca-Monophore A23187 (10 to 10 M) were significantly attenuated in atherosclerotic arteries. In deendothelialized tissues these compounds had no effect. In contrast, endothelium-independent relaxations induced by isoprenaline (10 to 10 M) were not affected by atherosclerosis. Atherosclerotic arteries showed also normal relaxations with high concentrations of glyceryl trinitrate (10 to 10 M), but reduced relaxations with a lower concentration of the compound (10 M). Acetylcholine (10 to 10 M) only produced endothelium-dependent relaxations in 8 of 60 arterial preparations (with or without atherosclerosis). In. most of the arteries, it was a direct vasoconstrictor (which may have masked EDRF release in many cases). Omission of indomethacin from the bath solution increased the incidence of moderate acetylcholine-induced relaxations (9 of 16 preparations). It is concluded that atherosclerosis attenuates EDRF-mediated vasodilation in epicardial human coronary arteries and that this impairment could promote coronary vasospasm and myocardial ischemia. |
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ISSN: | 0009-7330 1524-4571 |
DOI: | 10.1161/01.res.62.2.185 |