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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



esis. Moreover, as we have seen, exercise hyperemia 

 occurs in muscles poisoned with moniodoacetic acid 

 although their pH probably increases (112). 



All workers are agreed as to the great vasodilator 

 power of ATP and its related compounds in animals 

 (88, 162, 171) and man (70). And several have sug- 

 gested that it is concerned with exercise hyperemia. 

 In fact the amount of ATP in muscle is probably- 

 reduced in exercise because of conversion to ADP. 

 As we have seen the rate of the blood flow in muscle 

 closely parallels the rate of its oxygen usage. But so 

 far as I know there is no relation between muscle 

 2 consumption and the rate at which ATP or ADP 

 leaks out of the muscle fiber. 



Dawes (65) suggested that potassium might be 

 partly responsible for the hyperemia of exercise. This 

 was based on the finding that intra-arterial injection 

 of 5000 ^g of potassium into the pump-perfused 

 muscles of the dog's hind legs caused some vasodilata- 

 tion. Once more attention is being focused on potas- 

 sium. Kjellmar (130) found that postcontraction 

 hyperemia in the cat's gastrocnemius muscle was 

 accompanied by a rise in the potassium concentra- 

 tion in the venous effluent. Intra-arterial infusions of 

 small amounts of potassium caused vasodilatation. 

 But, and this is important, infusions of amounts far 

 bigger than those found during exercise cause con- 

 striction. Tetanus of the cat's muscle during the 

 potassium-induced constrictor phase was no longer 

 followed by hyperemia, although injected vaso- 

 dilator agents induced vasodilator responses. This 

 suggests that the hyperemia of exercise may be at 

 least partly due to the action of potassium ions. I do 

 not know whether the rate at which K leaves the 

 skeletal muscle fibers is related to their rate of oxygen 

 consumption. We have seen how closely blood flow 

 is related to oxygen consumption and to the work 

 done. 



Anrep and others (8, 9, 1 1 ) found that blood from 

 active muscles contained histamine and that during 

 contraction the amount of histamine in muscle di- 

 minished. Fleisch & Weger (87) repeated their 

 experiments and concluded that the loss of histamine 

 was due to the fact that the condition of the animals 

 had deteriorated. In man, active muscles do not 

 release a vasodilator substance, or if they do it does 

 not survive a single passage through the lungs. The 

 performance of leg exercise is not accompanied by 

 any change in the vascular resistance of the nerve- 

 blocked forearm (42). 



Bradykinin has recently come very much to the 



lore. Hilton (123) has shown that it is not implicated 

 in the mechanism of exercise hyperemia. 



In exercise muscle blood flow may increase ten- 

 fold. Peripheral vascular resistance in the muscle 

 must have fallen to one-tenth of its normal value and 

 the principal resistance vessels, usually considered to 

 be the arterioles, must be widely dilated. This dilata- 

 tion results from the action of metabolites produced 

 either in the arterial tree itself or in the surrounding 

 skeletal muscle fibers or in both. The question arises, 

 if metabolites from the skeletal muscle fibers are 

 involved, by what mechanism do they cause relaxa- 

 tion of the multilayered arteriolar plain muscle 

 coat? The following points seem relevant: 



1) It is not hard to imagine that vasodilator 

 metabolites from the tissue fluids could quickly 

 diffuse through the arteriolar walls. A good example 

 of diffusion through thick tissues is that of a dental 

 anesthetic, which in a short time seeps from the sub- 

 cutaneous tissue of the gum through the maxillary 

 bone into the tooth socket. Diffusion of metabolites 

 through minute arterioles might well be very rapid 

 indeed. 



2) Schretzenmayr (172) made the curious dis- 

 covery that contractions of the skeletal muscles in the 

 lower part of the cat's leg are followed by increase 

 in the diameter of the femoral artery in the inguinal 

 region. Figure 25 illustrates this. Since this increase 

 in diameter was not abolished by denervation, but 

 was by painting the vessels with phenol, he thought 

 that it must be an axon reflex from the active muscles 

 to the arterial walls. Fleisch (84) confirmed this in 

 the dog and showed that intra-arterial injections of 

 acetic acid, of various intermediary products of 



30 SEC 



fig. 25. Exercise of the leg muscles by stimulation of the 

 sciatic nerve (A, between the arrows) caused dilatation of the 

 femoral artery proximal to the muscle. After curare neither 

 stimulation of the sciatic {B) nor of the muscle (C) had any 

 effect on the diameter of the femoral artery. [From Hilton 



(122)-] 



