Membrane Physiological Reactions of Human Arteriosclerotic Coronary Arteries to Hypoxia

Abstract

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 mm Hg. 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 dilation at 30 mm Hg PO2 by about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relationship was quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronary arteries. The remainder could be attributed to the basal release of the endothelial dilator 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 accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. Hyperpolarization of 2.5 mV reduces the tension developed by one-half.