CIRCULATION IN SKELETAL MUSCLE 



'373 



metabolite from the skeletal muscle fibers (17). 

 Secondly, a perfectly normal initial vasodilatation 

 has been recorded in a patient whose muscles, owing 

 to an inborn error of metabolism, contained no 

 phosphorylase, so that the vasodilatation was prob- 

 ably not due to any product of glycolysis (146, 170; 

 also H. Barcroft and B. McArdle, unpublished ob- 

 servation). It seems reasonable to conclude that the 

 initial vasodilatation is not due to the action of 

 adrenaline on carbohydrate metabolism in the 

 skeletal muscle fibers, and that it probably is due to 

 the direct action of adrenaline on the plain muscle 

 of the arteriolar walls. 



Now we must consider the second part of the bi- 

 phasic initial transient vasodilatation — the rapid 

 return of the flow from the peak toward the resting 

 level. Allwood & Ginsburg (7) and de la Lande & 

 Whelan (136) have shown that this is due to a direct 

 constrictor action of adrenaline on the muscle vessels. 

 It can be partially or completely prevented by adre- 

 nergic blocking agents, as is shown in figure 20. That is 

 to say adrenaline causes first vasodilatation in muscle 

 almost immediately followed by vasoconstriction, 

 which can be prevented by a blocking agent. The 

 question now arises as to whether the vasodilator and 

 vasoconstrictor phases of the initial transient vaso- 

 dilatation take place in the same vascular bed, or is 

 the opening of one set of vessels soon followed by the 

 closing of another set in parallel? A little considera- 

 tion of the extent of the changes in flow shows that 

 the initial vasodilatation and the ensuing vasocon- 

 striction must both take place in the same set of 

 vessels. Suppose, as often happens, the flow before 

 the beginning of the infusion was 3 ml per min. 

 Then constriction in one bed could not reduce the 

 flow by more than the preinfusion rate of 3 ml. In 

 fact typical flows before, at, and after the initial 

 transient vasodilatation may be 3, 15, 6 ml, respec- 

 tively. That is, constriction may reduce the flow by 

 9 ml, i.e., by three times the total preinfusion rate. 

 Plainly this could only happen if the vessels had first 

 dilated so that they could be constricted to this 

 extent. 



It is well known that the action of adrenaline on a 

 piece of smooth muscle can be biphasic (45). It is 

 highly probable that the vasodilator and constrictor 

 phases of the initial transient vasodilatation are 

 both due to a direct biphasic action of adrenaline on 

 the smooth muscle coat of the arterioles of the skeletal 

 muscle vessels. This would be in accordance with 

 the fact that vasodilatation invariably comes before 

 constriction and that in any given infusion the sizes 



Minutes 



fig. 20. Results showing that the rapid return of the forearm 

 blood flow from the initial peak towards the resting rate during 

 adrenaline infusions is due to a direct vasoconstrictor action on 

 the muscle blood vessels. Open circles: before chlorpromazine. 

 Solid circles: after chlorpromazine. [From de la Lande & Whelan 



(136).] 



of the vasodilatation and vasoconstriction are usually 

 equal. If the inhibitory and excitatory actions of 

 adrenaline were to take place in different parts of 

 the same vascular bed, i.e., in the arterioles and 

 venules, it seems less likely vasodilatation would so 

 closely relate to constriction in both time and extent. 

 It is very difficult to imagine that the main resistance 

 could shift from the arterioles to the venules. It is 

 generally believed that adrenaline does constrict 

 arterioles. 



We must now turn to the smaller sustained vaso- 

 dilatation that follows the large initial transient one. 

 Similar sustained vasodilatation in muscle would be 

 expected to accompany a continuous release of adren- 

 aline from the adrenal glands. It will be recalled that 

 Celander (55) observed sustained vasodilatation 

 during intra-arterial adrenaline infusions and at- 

 tributed it to the action of lactic acid liberated by the 

 metabolic action of adrenaline in the skeletal muscle 

 fibers. Intra-arterial infusions of adrenaline in man 

 are also accompanied by local release of lactic acid 

 (6) and the small sustained vasodilatation in such 

 infusions may be due to an indirect metabolic action 

 of adrenaline on the skeletal muscle fibers. The evi- 

 dence so far available shows that the sustained vaso- 

 dilatation in man is rather larger during intravenous 

 than during intra-arterial infusions (29, 74, 177). 

 Celander (55) found the same in animals and thought 

 that it was because during intravenous infusions the 



