'44-8 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



two substances in the dog and the cat found nor- 

 epinephrine to be the more potent (see below). 



Two groups of workers (65, 118) have observed a 

 secondary increase in blood flow in the dog intestine 

 following the primary vasoconstriction due to epineph- 

 rine administration, although in the cat, Folkow et 

 al. (47) could find the constrictor effect only. Several 

 studies (35, 47, 65) have shown that only vasodilation 

 occurs with epinephrine if given after such substances 

 as ergotoxine, Dibenamine, or Ilidar. These same 

 substances are capable of blocking the constrictor 

 effect of norepinephrine but do not reverse it. 



Not all the results of investigations of volume or 

 weight changes of the intestine under the influence of 

 epinephrine and norepinephrine agree with the 

 findings on blood flow. Woods et al. (139), Goetz 

 (57) and MacLean et al. (96) all found that epineph- 

 rine caused a primary reduction in volume followed 

 by a secondary increase. The latter observed a de- 

 crease in weight with norepinephrine. Opposed to 

 these are the observations of Biilbring & Burn (25), 

 Goetz (57), with small doses, and Burn & Hutcheon 

 (26) that epinephrine increased the volume oi in- 

 testinal segments of dogs and cats. As Folkow (48) 

 has stated, these discrepancies might well be ex- 

 plained by the possibility that the smooth muscle 

 relaxing effects of epinephrine result in a decreased 

 transmural pressure in the intestinal vessels which for 

 small doses of the drug overbalance its usual con- 

 strictor effects. Aside from this possibility, it remains 

 highly questionable whether or not intestinal vascular 

 resistance changes can be deduced from variations in 

 the volume of the organ. 



The influence of the parasympathetic portion of 

 the autonomic nervous system on the intestinal 

 vasculature is not completely clear. Celander & 

 Folkow (32) observed an increase in intestinal blood 

 flow in the cat as a part of the depressor response to 

 sinus nerve stimulation. Since this disappeared after 

 ergotamine, they concluded that there were no 

 dilator fibers involved and that the increase in flow 

 was the consequence of a reduction in constrictor 

 tone. The parasympathetic mediator, acetylcholine, 

 does seem to cause vasodilation, as shown by the 

 just-mentioned workers, as well as by Binit et al. 

 (15) and by Bean & Sidky (13). The latter took great 

 care to separate the effects of the compound on the 

 vasculature and the visceral smooth muscle and 

 showed that the increase in blood flow appeared 

 before the augmentation of motor activity. The 

 increase in blood flow was abolished or reversed by 

 vigorous segmental contractions. Howe\ er, one note 



of caution should be made regarding all three of 

 these studies. All were performed with perfused 

 preparations and it may be that the control blood 

 flows were abnormally low as is so frequently the 

 case with perfused intestinal segments. Although 

 adequate control data are not given in any instance, 

 estimations from Bean and Sidky's results indicate 

 that their preparations may have had an abnormally 

 high constrictor tone. Care should be exercised, 

 therefore, in concluding that acetylcholine has a 

 dilator effect in the intact normally perfused in- 

 testine. 



It seems reasonable to conclude that splanchnic 

 nerve stimulation, and administration of the adrener- 

 gic substances, epinephrine and norepinephrine, 

 produce vasoconstriction in the intestine, presumably 

 by excitation of alpha adrenergic constrictor re- 

 ceptors as reviewed by Green & Kepchar (66a). 

 The usual secondary dilation observed after epineph- 

 rine injection and especially the primary dilation 

 seen when epinephrine is administered following 

 Ilidar or ergotamine blockade indicates the presence 

 of beta adrenergic dilator receptors as well. This 

 offers an explanation of the lesser constrictor potency 

 of epinephrine since this compound, unlike nor- 

 epinephrine, stimulates both the constrictor and 

 dilator receptors. The small increase in flow which 

 occurs during splanchnic stimulation after admin- 

 istration of Ilidar or ergotamine seems more likely 

 to be explained by intestinal smooth muscle relaxa- 

 tion, or by mechanical distention of blood vessels 

 due to a rise in blood pressure, than by stimulation of 

 the beta dilator receptors. It is highly questionable 

 whether the vagus has any influence on the intestinal 

 circulation other than that secondary to augmenta- 

 tion of motor activity. Acetylcholine probably has a 

 dilator effect but unequivocal proof of this in the 

 intact intestine is not available. 



The influence of other chemical compounds on the 

 intestine may be summarized as follows. Biilbring & 

 Burn (25) found histamine to produce a slight vaso- 

 dilation, as did Binit et al. (15). In this writer's 

 laboratory, on the other hand, this compound has 

 been found to produce constriction fairly consistently 

 in artificially perfused intestinal segments. Both 

 Selkurt's group (121) and Bohr and his colleagues 

 (19) found serotonin to be an intestinal vasocon- 

 strictor. The latter also found Pitressin to be a con- 

 strictor of intestinal surface vessels. 



Vasodilation has been produced by isopropylnor- 

 epinephrine in the hands of Green et al. (65), by 

 curare in a study by Elwell & Bean (42), by adenosine 



