Vasodilation is induced by potassium, inorganic phosphate ions, and interstitial fluid osmolarity. These factors may contribute to active hyperemia, which is an increase in blood flow caused by enhanced tissue activity. However, significant increases in phosphate concentration and osmolarity are not always observed during muscle contraction, and they may only transiently increase blood flow. Therefore, they are unlikely to mediate the vasodilation observed during muscular activity.

Potassium is released at the onset of skeletal muscle contraction or with an increase in cardiac muscle activity. This release of potassium could explain the initial decrease in vascular resistance seen in response to physical exercise or increased cardiac work. However, the release of potassium is not sustained, yet arteriolar dilation persists throughout the period of enhanced muscle activity. Additionally, when reoxygenated venous blood obtained from active cardiac and skeletal muscles is infused into a test vascular bed, it does not cause vasodilation. This suggests that oxygenation of venous blood does not alter its potassium or phosphate content or its osmolarity, thus neutralizing its vasodilator effect. Therefore, there must be another agent responsible for mediating the vasodilation associated with metabolic activity of the tissue.

Adenosine, which plays a role in regulating coronary blood flow, may also participate in controlling the resistance vessels in skeletal muscle. Furthermore, certain prostaglandins may act as important vasodilator mediators in specific vascular beds. Many prostaglandins have been proposed as mediators of metabolic vasodilation, but further research is needed to determine the relative contribution of each.

The release of a vasodilator substance for metabolic control of vascular resistance requires the presence of basal vessel tone. While tone in vascular smooth muscle is independent of the nervous system, tonic activity is evident. Therefore, some metabolic factor must be responsible for maintaining this tone. Possible factors include the myogenic response to blood pressure-induced stretch, the high partial pressure of oxygen in arterial blood (PaO2), or the presence of calcium ions (Ca++).

When arterial inflow to a vascular bed is temporarily stopped, reactive hyperemia occurs upon release of the occlusion. Reactive hyperemia is an increase in blood flow that exceeds the flow prior to occlusion and gradually returns to the control level. This phenomenon supports the existence of a local metabolic factor that regulates tissue blood flow.

In an experiment involving the clamping of the femoral artery in the leg, blood flow was stopped for 15, 30, and 60 seconds. Upon release of the 60-second occlusion, peak blood flow was 70% greater than the control flow, and the flow returned to the control level within 110 seconds.

The duration of reactive hyperemia and the peak flow are generally proportional to the duration of the occlusion. If the extremity is exercised during the occlusion period, reactive hyperemia is increased. These observations, along with the close relationship between metabolic activity and blood flow in an unoccluded limb, support the idea of a metabolic mechanism in the local regulation of tissue blood flow.
Potassium, inorganic phosphate ions, and interstitial fluid osmolarity induce vasodilation. During skeletal muscle contraction, both (1) K+ and phosphate are released and (2) osmolarity is increased. Therefore, these factors may contribute to active hyperemia (increase in blood flow caused by enhanced tissue activity). However, significant increases in the phosphate concentration and in osmolarity are not always observed during muscle contraction, and they may increase blood flow only transiently. Therefore, they probably do not mediate the vasodilation observed during muscular activity.
Potassium is released at the onset of skeletal muscle contraction or with an increase in cardiac muscle activity. Hence, release of K+ could underlie the initial decrease in vascular resistance observed in response to physical exercise or to increased cardiac work. However, release of K+ is not sustained, but arteriolar dilation persists throughout the period of enhanced muscle activity. Furthermore, reoxygenated venous blood obtained from active cardiac and skeletal muscles does not elicit vasodilation when the blood is infused into a test vascular bed. It is unlikely that oxygenation of venous blood alters its K+ or phosphate content or its osmolarity and thereby neutralizes its vasodilator effect. Therefore, some agent other than K+ must mediate the vasodilation associated with metabolic activity of the tissue.
Adenosine, which contributes to the regulation of coronary blood flow, may also participate in control of the resistance vessels in skeletal muscle. In addition, some prostaglandins may be important vasodilator mediators in certain vascular beds. Many prostaglandins have thus been
CHAPTER 18 Regulation of the Heart and Vasculature proposed as mediators of metabolic vasodilation, and the relative contribution of each remains to be determined.
Metabolic control of vascular resistance by the release of a vasodilator substance requires the existence of a basal vessel tone. Tonic activity in vascular smooth muscle is readily demonstrable, but in contrast to tone in skeletal muscle, the tone in vascular smooth muscle is independent of the nervous system. Thus some metabolic factor must be responsible for maintaining this tone. The following factors may be involved: (1) the myogenic response to the stretch imposed by blood pressure, (2) the high partial pressure of oxygen in arterial blood (PaO2), or (3) the presence of Ca++ .
If arterial inflow to a vascular bed is stopped temporarily, blood flow on release of the occlusion immediately exceeds the flow that prevailed before occlusion, and the flow gradually returns to the control level. This increase in blood flow is called reactive hyperemia. This type of event provides evidence for the existence of a local metabolic factor that regulates tissue blood flow.
In the experiment shown in
Fig. 18.23 , blood flow to the leg was stopped by clamping of the femoral artery for 15, 30, and 60 seconds. Release of the 60-second occlusion resulted in a peak blood flow that was 70% greater than the control flow, and the flow returned to the control level within 110 seconds.
Within limits, peak flow and particularly the duration of reactive hyperemia are proportional to the duration of the occlusion (see
Fig. 18.23 ). If the extremity is exercised during the occlusion period, reactive hyperemia is increased. These observations and the close relationship between metabolic activity and blood flow in an unoccluded limb are consistent with the notion of a metabolic mechanism in the local regulation of tissue blood flow.
•Fig. 18.23 Graphsofreactivehyperemiainthehindlimbofthelegafter15-,30-,and60-secondocclusionofthefemoralartery.(FromBerneRM.Unpublishedobservations.)0 2 4 6 8 10 0 20 40 60 80 100 Time (min) Femoral blood flow(mL/min) 0 20 40 60 80 100 120 Femoral arterial pressure(mm Hg)
Coordination of Arterial and Arteriolar Dilation