224 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



MAX CONSTRICTION 

 100 



BASAL 

 BLOOO FLOW 



PHYSIOL DISCHARGE RANGE 



JSTIM 

 30 FREQ 



FIG. 9- Vasoconstrictor effect of electric stimulation of lumbar sympathetics at \arying frequencies 

 in the cat. Striped area indicates the variations obser\'ed in 40 experiments. A represents a\'erage of 

 10 experiments with the biggest response; B, average response after vasodilator drugs. [From Folkow 

 (46).] 



The effect of stimulation at various frequencies of 

 sympathetic nerves to the muscular Ijlood vessels in 

 the lower part of the hind limlj of the cat has been 

 measured by recording the outflow (46). 



Figure 9 shows the correlation between stimula- 

 tion rate and the constrictor response. It is clearly 

 seen that low stimulation frequencies are very effec- 

 tive. This applies also to cutaneous blood vessels (22). 



A detailed analysis of the mechanism of the release 

 has been made by Brown & Gillespie (14) using the 

 cat's spleen. Samples of venous blood were collected 

 and the norepinephrine content assayed on the ar- 

 terial pressure of the pithed rat. Supramaximal 

 stimuli were applied to the splenic nerve, the total 

 number of stimuli being 200, irrespective of the fre- 

 quencv. Both adrenal glands were removed and the 

 splanchnic nerves cut. The output of norepinephrine 

 was expressed as amount released per stimulus. 



As illustrated in figure io.4 the norepinephrine out- 

 put per stimulus was low at low frequencies, but as 

 the frequency increased the amount found in venous 

 blood rose sharply to a maximum at about 30 stimu- 

 lations per sec. Since the output per stimulus was 

 the same before and after addition of isopropyl 

 isonicotinyl hydrazine (Marsilid), an effect of amine 

 oxidase on the transmitter liberated at lower frequen- 

 cies could be excluded. The possibility was also dis- 

 cussed that, although the amount of transmitter re- 

 leased by each nerve volley might be constant, more 

 was 'utilized' by tissue receptors at a low rate of stim- 



ulation. After blocking tissue receptors with N-N- 

 dibenzyl-/3-chloroethylamine (dibenamine), it was 

 found that the output per impulse reaching the blood 

 was greatly increased at the lower frequencies and 

 maintained a constant value at different frequencies. 

 From these observations it was concluded that the 

 norepinephrine release per nerve volley is constant 

 and that the fraction removed by the tissues is 

 greater at the lower frequencies of stimulation (cf. 

 section on removal of transmitter, p. 227). 



The experiments quoted above may have an in- 

 teresting implication in that the small or absent over- 

 flow at low stimulation frequency (or adrenergic 

 nerve activity) and the larger overflow at higher ac- 

 tivity may cause an excretion pattern in the urine 

 which 'amplifies' the actual release and makes differ- 

 ences more pronounced than would be expected from 

 the activity of the effector. 



EFFECTS ON REMOTE ORGANS. This method of study- 

 ing the release of the adrenergic transmitter is the 

 one which led to the discovery and demonstration of 

 such a mechanism. The first experiments of this kind 

 were made by Cannon & Uridil in 1921 (21) who ob- 

 served the effect of stimulating the li\cr nerves on the 

 heart and iris .sensitized by denervation. They as- 

 cribed the effect to a "special and unknown sub- 

 stance" apparently being set free by the stimulation. 

 This kind of experiment was developed further by 

 Cannon and Rosenblueth and their co-workers in the 



