Endothelial dysfunction in human atherosclerotic coronary arteries.

Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mmHg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mmHg PO2 by about 51%. The reduction was 27% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (73% in arteriosclerotic coronaries) restriction of dilatory vascular reactivity. The relationship was quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory contribution of prostacyclin was 32% in normal and 12% in arteriosclerotic coronary arteries. The remainder could be attributed to the basal release of endothelium-derived hyperpolarizing factor (EDHF). Thus, it may be concluded that in arteriosclerotic blood vessels, prostacyclin (PGI2) synthesis and release are predominantly diminished. Finally, we found that the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In addition, a disturbed transmembrane cation distribution in the arteriosclerotic coronary vessels may be an additional explanation for the depolarized membrane potential and increased muscle tone. [Na+]i of normal arteries amounted to 16.6, of arteriosclerotic arteries to 60.9 mmol.l-1; [K+]i values were 134.6 in normal and 95.0 mmol.l-1 in arteriosclerotic coronaries, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)