CENTRAL CARDIOVASCULAR CONTROL 



1133 



thetic paravertebral ganglia and hence are not 

 reached on extirpation of the latter [VVrete (226-228), 

 Pick & Sheehan (174), Alexander et al. (11), Boyd & 

 Monro (38), Randall et al. (178)]. A greatly reduced, 

 though functional, central vasoconstrictor control 

 might therefore persist even after 'total' sympa- 

 thectomy. If so, then we would have an explanation 

 of some obscure earlier observations of extremely slight 

 but undoubted carotid sinus reflex responses per- 

 sisting after "sympathectomy' [e.g. Bacq et al. (22)]. 



CHEMICAL TRANSMISSION. This article is not the place 

 for extensive discussion of chemical transmission prob- 

 lems; the more so as Clhapter VII of this Handbook 

 by von Euler is devoted to this subject; in addition, 

 several very instructive reviews have been published, 

 such as those of von Euler (207-210) and Holtz (129). 

 Only a few words will be said about the chemical 

 transmitter at the vasoconstrictor nerve terminals. 



Norepinephrine is considered to be the main 

 transmitter at postganglionic adrenergic nerve ter- 

 minals. As regards the vasoconstrictor nerve terminals, 

 however, the evidence that norepinephrine is the 

 transmitter is indirect and rests chiefly on our knowl- 

 edge of the vascular effects of norepinephrine and 

 epinephrine. 



Epinephrine and norepinephrine both have a pure 

 vasoconstrictor action on some vessels, e.g. those of 

 the skin and intestines. In skeletal muscle vessels epi- 

 nephrine has a dual action. In low concentrations it 

 has a vasodilator, in higher concentrations a vaso- 

 constrictor, action. Under the influence of sympa- 

 tholytic drugs, such as ergotamine, the vasoconstrictor 

 action is blocked and even high doses of epinephrine 

 produce vasodilatation. Norepinephrine, on the other 

 hand, has a purely constrictor effect even on skeletal 

 muscle vessels. Its vasoconstrictor effect is completely 

 blocked by sympatholytic drugs without any vaso- 

 dilator action emerging, as shown by Hartman (114), 

 Clark (59), Folkow et al. (83) and Youmans et al. (230). 



Folkow & Uvnas (90, 91) presented experiments 

 on cats to show that the transmitter liberated by 

 vasoconstrictor reflexes was devoid of a \'asodilator 

 action on blood vessels. In contrast to the constrictor 

 effect of epinephrine, but in common with that of 

 norepinephrine, the action of the vasoconstrictor 

 transmitter could be completely blocked but not re- 

 versed by sympatholytic drugs. Hence the transmitter 

 could not plausibly be identified with epinephrine, 

 but was probably norepinephrine. The obserxation 

 by Schmiterlow (190) that the arterial walls contain 



almost solely norepinephrine is consistent with such 

 an assumption. 



In the opinion of Lundholm (158) the vasodilator 

 effect of epinephrine is secondary to lactic acid pro- 

 duction caused by epinephrine in the muscles. The 

 vasodilatation is thought to be produced by the accu- 

 mulated lactic acid. It should be borne in mind, 

 however, that conclusions as to the chemical nature 

 of the transmitter substance which are based on ob- 

 servations of its vascular effects after intravenous or 

 intra-arterial administration do not possess any 

 major evidential value. In contrast to intravascularly 

 administered epinephrine, the epinephrine which, 

 under physiologic conditions, is liberated at the vaso- 

 constrictor nerve terminals, does not diffuse into the 

 surrounding skeletal muscle but probably has merely 

 a local action round the site of the neuroeffector 

 junction. Such a local vascular effect of epinephrine 

 might well be exclusively vasoconstrictor. [For further 

 information, see Folkow et al. (83) and von Euler 

 (210).] 



The chemical transmission at the coronary vaso- 

 constrictor nerve terminals has been the subject of 

 extensive discussion. Since both epinephrine and 

 norepinephrine given intravascularly lead to an in- 

 creased coronary blood flow, it has been considered 

 that they cannot be transmitter substances at vaso- 

 constrictor nerve terminals. It has consequently been 

 repeatedly hypothesized that the coronary vessels 

 are supplied by parasympathetic vasoconstrictor 

 nerves with acetylcholine as transmitter [Anrep & 

 Segall (17), Gollwitzer-Meier & Kriiger (loi), Esse.x 

 et al. (79), Gregg & Shipley (iio)]. Since both epi- 

 nephrine and norepinephrine, on intravascular ad- 

 ministration, produce a substantially increased myo- 

 cardial activity which is known to lead to an elevated 

 coronary flow, it is possible although not proved that 

 norepinephrine might have a purely constrictor effect 

 if it could be injected locally into the coronary wall 

 muscle without diffusing into the cardiac tissue. 



Several authors, such as Greene (108), asserted 

 that the vagus nerves contain adrenergic fibers to the 

 heart. In addition to accelerator fibers the vagal ad- 

 renergic outflow might contain coronary constrictor 

 fibers, as suggested by Greene. Acetylcholine has a 

 marked vasodilator action on the coronary vessels, 

 according to Folkow et al. (84), and cannot serve as 

 a constrictor mediator. It is plausible, therefore, to 

 assume for the time being that norepinephrine or 

 (less probably) epinephrine is the transmitter at the 

 coronars constrictor ner\'e endings. The coronary 



