Efficient peripheral oxygen delivery requires tight regulation of blood flow distribution. Impairment of normal vascular control is manifest in tissues exhibiting pathological supply dependence of oxygen transport. For example, alpha-receptor blockade is associated with a decline in the ability of the body as a whole to extract oxygen from a limited supply. It was hypothesized later that a within-organ defect in blood flow related to an abnormal vascular reactivity may account for impaired organ oxygen regulation. Consistent with this hypothesis, we have developed an
in vivomethod for stripping the canine hindlimb vascular endothelium and have shown that this was associated with severe limitation in oxygen extraction ability. We have observed that double block of the endothelial vasodilators nitric oxide and prostacyclin caused a significant decrease in the ability of canine skeletal muscle to extract oxygen during ischemic hypoxia, although nitric oxide does not appear to be preponderant in increasing oxygen extraction. We concluded from these results that vascular endothelium plays an essential role in the defense of tissue oxygenation when oxygen supply to resting muscle is reduced.
In an
in vitrostudy we showed the determining contribution of ATP-sensitive K
+channel-mediated hypoxic vascular smooth muscle relaxation. We further verified that ATP-sensitive K
+channel-mediated hyperpolarization and vasodilation during hypoxia is essential to adjust oxygen transport to meet oxygen demand. We propose that this is consistent with studies in which hyperpolarization or depolarization is conducted bidirectionally along arterioles for several millimeters and display functional characteristics that are appropriate for controlling the distribution and magnitude of blood flow and red blood cells content in a select group of capillaries and thereby enhance the oxygen supply to localized regions of the microvascular network.
These findings are consistent with the hypothesis that impairment of tissue autoregulation of blood flow distribution is linked to impairment of vascular control. Although this hypothesis remains speculative, its offers a new approach to understanding the genesis of extraction defects in peripheral tissues.
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