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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



muscle (see 1 16, 147). Many of the results are difficult 

 to interpret. Artificial perfusion pumps, often used in 

 these studies, must have damaged the blood and, 

 because of the release of vasodilator substances, 

 basal tone in the muscle vessels may be weakened 

 (91). About the use of artificial pumps Folkow (91) 

 says "The present experiments indicate that slight 

 interference with the blood supply may damage the 

 blood cells with release of substances that consider- 

 ably depress the tone of the vascular smooth muscles 

 and their reactions to different types of stimuli. 

 The mere passage of normal arterial blood through a 

 pump device of the type generally used in the per- 

 fusion experiments releases these substances in con- 

 centrations big enough to depress the vascular tone. 

 The rougher the handling of the blood the bigger 

 will their effect* be .... The substance (or substances) 

 is contained in the blood cells, probably in the eryth- 

 rocytes, and is rapidly destroyed while passing the 

 lungs, even when present in big concentrations .... 

 It must be a very potent vasodilator agent, as the 

 erythrocytes of only 0.5 mm 3 blood contain amounts 

 enough to elicit a well-defined vasodilatation .... 

 All these characteristics are typical also for ATP. 



"It should be stressed, that most blood pump 

 devices are very unsuitable for a study of the reactions 

 of the blood vessels, as their vascular smooth muscles 

 rapidly loose their tone and reactivity to most kinds 

 of influences due to the fact that big amounts of 

 vasodepressor agents are then released from the 

 formed elements of the blood. . . ." These remarks 

 apply to the cat (Folkow, personal communication). 



Besides being observed during pump perfusion, 

 the action of adrenaline was usually studied after 

 the hormone had been given rapidly by single 

 injection, so that there was not enough time for the 

 resulting action on the vessels to reach a steady 

 state. 



Dale & Richards (63, 64), in two classic papers, 

 showed that small doses of adrenaline cause vaso- 

 dilatation in the denervated muscles of the cat's 

 hind limb. 



Clarke (57, 58) gave adrenaline by intra-arterial 

 infusion. His records of the venous outflow from the 

 skinned limb of the cat show that it had a biphasic 

 effect — vasodilatation followed by vasoconstriction. 

 The vasodilator effect has been attributed to libera- 

 tion of acetylcholine (174, 175), but this has been 

 denied. Celander (55) recorded the changes in 

 venous outflow from the denervated muscle of the 

 cat's hind leg. Close intra-arterial infusion of adren- 

 aline at 0.04 fig per kg per min had no effect (fig. 1 7 A) ; 



0.07 fig per kg per min caused a large transient 

 dilatation accompanied by a small sustained one 

 lasting till the end of the infusion (fig. 17C); 0.13 

 fig per kg per min caused the initial transient vaso- 

 dilatation followed, in this case, not by sustained 

 vasodilatation but by sustained constriction (fig. 

 175). Whether the initial transient vasodilatation 

 was followed by small sustained vasodilatation or by 

 sustained vasoconstriction was a matter of dosage. As 

 to the explanation of this paradox Celander says: 

 "It is hard to conceive that the direct effect of /-adren- 

 aline on the smooth muscle cells of the muscular blood 

 vessels at a low dosage should be relaxation while the 

 same substance on the same substrate at a higher dos- 

 age would bring about a constriction. It seems more 

 reasonable to assume that the dilator action of 

 /-adrenaline is an "indirect" one and that its disap- 

 pearance at a higher dosage of /-adrenaline is related 

 to the 'direct' constrictor action of /-adrenaline. In 

 that case the dilatation would be due to the mobiliza- 

 tion of a vasodilator factor released by /-adrenaline 

 in the surrounding; skeletal muscle cells with a sec- 

 ondary influence on the smooth muscles of the blood 

 vessels." The author thought that the sustained vaso- 

 dilatation was a phenomenon which should be looked 

 upon more as a "metabolic" action of adrenaline 

 than as a direct "motor" action. He also thought 



BLOOD 

 PRESSURE 



MUSCULAR 

 BLOOD FLOW 



SIGNAL 

 TIME-30SEC 



fig. 17. Effects on muscular blood flow of /-adrenaline given 

 intra-arterially. Perfusing blood pressure 120 mm Hg. Body 

 weight 2.5 kg. A: I -A infusion /-adrenaline 0.04 jig/kg/min. 

 B. I -A infusion /-adrenaline 0.13 jig/kg/min. C: I-A infusion 

 /-adrenaline 0.07 jig/kg/min. For further details see text. 

 [From Celander (55).] 



