Is the Cellular Thiol-Disulfide System Involved in Oxygen Sensitivity of Arterial Contraction?

The partial pressure of oxygen (Po2) is a known factor in the autoregulation of local blood flow adjusting the oxygen supply to its demand within the cells. This phenomenon of the oxygen-dependent tone of vascular smooth muscle is found not only at the level of the resistance vessels but also in several large arteries and means (with the exception of pulmonary vessels) a decreased contractility at lowered Po2 and vice versa (1). Little is known about the signal chain connecting Po2 to smooth muscle contraction. Among other hypotheses it is discussed, that Po2 might influence contraction either by its direct effect on oxidative phosphorylation potential or by mediators originating from an impaired metabolism under hypoxic conditions: e.g., creatine, inorganic phosphate (Pi), adenosine, prostaglandins, or altered membrane potential (1–4). The function of the endothelium is controversial: some reports support its role as an oxygen sensor (5), and others rule out an endothelial function for hypoxic vasodilation (6). Further sensing mechanisms were ascribed to receptors apart from the vessel wall (1). Another basis for an oxygen sensor could be that cellular production of O 2 - and H2O2 is dependent on Po2 (7,8). The corresponding detoxifying system involves glutathione peroxidase, thus connecting Po2 to the thiol disulfide system. Since it has been shown in several biological systems that hydroperoxide metabolism or thiol oxidation induces Ca2+ liberation (911), and since we found hydroperoxide-and Po2-dependent alterations in the cellular thiol-disulfide system in arterial smooth muscle (11), we were interested whether these alterations could be involved in the signal chain by which Po2 can influence arterial contractility.