Smooth muscle cells in the arteriolar wall are exposed to the chemical composition of the interstitial fluid of the organ they serve. Interstitial concentrations of many substances reflect the balance between the metabolic activity of the tissue and its blood supply. Interstitial O2 levels, for example, fall whenever the tissue cells are utilizing O2 faster than it is being supplied to the tissue by blood flow. Conversely, interstitial O2 levels rise whenever excess O2 is being delivered to a tissue from the blood. Whenever blood flow and oxygen delivery fall below a tissue's O2 demand, the O2 levels around arterioles fall, the arterioles dilate, and the blood flow through the organ appropriately increases. Many substances in addition to O2 are present within tissues and can affect the tone of vascular smooth muscle. When the metabolic rate of skeletal muscle is increased by exercise, for example, not only does the tissue level of O2 decrease, but also the levels of CO2, H+, lactate, and K+ increase. Muscle tissue osmolarity also increases during exercise. All of these chemical alterations cause arteriolar dilation. In addition, with increased metabolic activity or oxygen deprivation, cells in many tissues may release adenosine (metabolite from ATP breakdown), which is an extremely potent vasodilator agent. Several factors may be involved in any given vascular bed, and different factors play significant roles in different tissues.
For conceptual purpose, our understanding of local metabolite control can be summarized as shown in Figure 3. Vasodilator factors enter the interstitial space of the tissue cells at a rate proportional to tissue metabolism. These vasodilators are removed from the tissue at a rate proportional to blood flow. Whenever tissue metabolism is proceeding at a rate for which the blood flow is inadequate, the interstitial vasodilator concentrations will build up and cause the arterioles to dilate and thus subsequently increase blood flow. This process will continue until the metabolic demand is matched by the increased blood flow. The same system also operates to reduce blood flow when it is higher than required by the tissue's metabolic activity, because this situation causes a reduction in the interstitial levels of metabolic vasodilators. With this in mind, the flow autoregulation phenomenon can be readily explained. For example, an increase in arterial blood pressure (increased perfusion pressure) will initially increase blood flow to a tissue or organ. This increased blood flow will "wash out" vasodilator substances in the area, and thus vascular resistance increases (arterioles now have decreased radius and increased tone) and blood flow returns to the normal resting level (Figure 3).