title: Role of prostacyclin in normal and arteriosclerotic human coronary arteries during 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. The isometric pretension was 2 g in all investigations. Two series of experiments, one with an application of indomethacin and another one with deendothelialized blood vessels, confirmed the hypothesis that the endothelium of arteriosclerotic coronary arteries arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mm Hg PO2 but 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 relation was quite similar for a carbogen Krebs solution (resting, control conditions). The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronaries. The rest can be attributed to the basal release of the endothelial dilator EDHR. Thus, it may be concluded that, in arteriosclerotic blood vessels, PGI2 synthesis and release are predominantly diminished or its effectivity is impaired. Finally we found 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. 2.5 mV hyperpolarization reduces the tension developed by half.
authors.affiliation: Institute of Physiology, Free University of Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Siegel
authors.forename: F
authors.initials: F
authors.lastname: Schnalke
authors.forename: K
authors.initials: K
authors.lastname: Rückborn
authors.forename: J
authors.initials: J
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Hetzer
mesh_terms: D001161:Arteriosclerosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology*; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D011464:Epoprostenol; D007213:Indomethacin