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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



vein with little or no action upon the arterial circuit. 

 Acetyl-/3-methylcholine chloride and carbaminoyl 

 chloride had a similar but longer action and did not 

 produce different responses depending upon the route 

 of administration, possibly because neither is readily 

 destroyed by hepatic esterases. In subsequent studies 

 of the effect of acetylcholine on the perfused hepatic 

 vasculature of the monkey, cat, and rabbit, the same 

 group (12) was impressed by the difficulty of obtaining 

 reproducible responses for "the vascular responses 

 showed considerable variation not only from species 

 to species but also from time to time in the same 

 animal." Similar equivocal results have been obtained 

 in studies of isolated gut (27). Indeed, Bean & Sidky 

 (27) have adduced evidence that the increase ob- 

 served in blood flow through a perfused intestinal 

 loop is attributable to the release of vasoactive ma- 

 terials locally rather than to a direct effect upon the 

 vasculature. In the case of the spleen, acetylcholine 

 does seem to have a direct effect at least insofar as 

 strips of splenic muscle are concerned (53). 



In his initial studies in 191 8, Reid Hunt found that 

 the liver of the intact dog shrank following intravenous 

 administration of small doses but expanded with 

 larger ones. A similar response was noted by 

 McMichael (210) in the cat; the reduction in volume 

 coincided with a fall in portal venous pressure and 

 arterial pressure. In a similar study of the dog, Katz 

 & Rodbard (182) also noted that acetylcholine caused 

 an isolated fall in portal venous pressure that occurred 

 at approximately the same time as a fall in arterial 

 pressure and a rise in peripheral venous pressure. 

 Portal venous flow (Ludwig stromuhr) tended to 

 follow the portal venous pressure but did not fall to 

 the same extent as arterial pressure, suggesting the 

 development of mesenteric arteriolar dilatation. In 

 more recent studies, the results also suggest that 

 vasodilatation may occur in the liver though a change 

 inflow has not been seen on direct observation (299). 

 Using implanted devices to measure flow, Ginsburg 

 & Grayson (147) and Gersmeyer & Gersmeyer (142) 

 report an increase in hepatic venous outflow in rats 

 and dogs during intravenous infusion of acetylcholine. 

 Since arterial pressure fell at the same time, intra- 

 hepatic resistance must have diminished. An increase 

 in the volume of the gut and in mesenteric and gastric 

 outflow has been noted by other workers (132, 219). 

 The increment in hepatic blood flow cannot be ex- 

 plained entirely on this basis, however, since Ginsburg 

 & Grayson (147) found that hepatic blood flow in- 

 creased in the rat even when portal drainage was 

 diverted from the liver. The spleen in the intact dog 



apparently changes little in volume with a slight 

 augmentation in arterial inflow despite arterial hy- 

 potension (164, 223). 



Although the reactions, outlined above, to acetyl- 

 choline in the isolated and intact hepatic vasculature 

 are obviously equivocal, a change of some kind does 

 seem to occur. This fact is a little difficult to square 

 with the absence of cholinergic innervation of the 

 splanchnic and hepatic vessels and with the lack of 

 any response to vagal neurectomy and stimulation. 

 Cholinergic activity is definitely important in the 

 function of the gastrointestinal musculature and of 

 the glands of the biliary tract and pancreas. Hence, 

 it is possible, as Bean & Sidky (27) have suggested, 

 that secondary release of substances acting locally 

 upon the blood vessels may be implicated. Brandon 

 & Rand (53) and Burn & Rand (6g) have recently- 

 brought forward a more attractive hypothesis that 

 acetylcholine may release norepinephrine from stores 

 in the tissues (in the nerves or chromaffin cells) which 

 may be depleted by reserpine or neural degeneration 

 and replaced by an infusion of norepinephrine. The 

 variability of the results reported by many workers 

 may well be explained, in part at least, by variation 

 in the stores initially available and in the depletion of 

 the neurotransmitter during the preparation of the 

 tissues for study. Stimulation of the adrenal medulla 

 and a general systemic response must also be taken 

 into account in the interpretation of the effect of 

 acetylcholine upon the hepatic circulation in the 

 intact animal. 



autonomic blockade. Autonomic denervation and 

 chemical interference with autonomic activity have 

 proved extremely helpful in the study of neurovascular 

 function. As knowledge has accumulated, however, 

 the complexities of the problem have become in- 

 creasingly apparent. Surgical denervation is neces- 

 sarily limited by the inaccessibility, diversity, and 

 versatility of the nerve supply. A remarkable array of 

 autonomic blocking agents is now available and grow- 

 ing in number and variety with each year. Unfortu- 

 nately, the supply has outrun the laborious and 

 gradual gathering of information regarding mode and 

 site of action. Most of these substances interfere with 

 both sympathetic and parasympathetic function, 

 most produce confusing side effects unrelated to the 

 splanchnic adrenergic blockade. Few have been 

 studied with special attention to the effects upon 

 hepatic inflow and outflow tracts. Since this is not the 

 place to embark upon a detailed examination of the 

 mechanisms of adrenergic and cholinergic blockade, 



