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 F2 alpha.
Indomethacin (10(-5) M) was present to prevent possible interference from endogenously formed
prostaglandins. The EDRF-mediated relaxations in response to
substance P (10(-10) to 10(-8) M),
bradykinin (10(-9) to 10(-7) M), and Ca2+-
ionophore A23187 (10(-9) to 10(-7) M) were significantly attenuated in atherosclerotic arteries. In deendothelialized tissues these compounds had no effect. In contrast, endothelium-independent relaxations induced by
isoprenaline (10(-7) to 10(-5) M) were not affected by
atherosclerosis. Atherosclerotic arteries showed also normal relaxations with high concentrations of
glyceryl trinitrate (10(-8) to 10(-7) M), but reduced relaxations with a lower concentration of the compound (10(-9) M).
Acetylcholine (10(-7) to 10(-6) 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 vasospasm and
myocardial ischemia.