THE HEPATIC CIRCULATION 



[ 4 I7 



be eliminated as a cause for myogenic activation (180). 

 The possibility that elevated hepatic venous pressure 

 may induce reflex constriction in the hepatic arterioles 

 and portal venules should be investigated. Similarly, 

 conclusive demonstration of reflex changes mediated 

 through spinal or corticothalamic centers via visceral 

 afferent and efferent arcs is needed. There is little 

 doubt that disturbance of splanchnic and hepatic 

 vessels or stimulation of the central ends of the cut 

 splanchnic nerves can give rise to marked changes in 

 systemic hemodynamics. In both man and experi- 

 mental animals traction on the mesenteric vessels is 

 associated with a striking fall in arterial blood pressure 

 provided the nerve supply is intact (230, 291), whereas 

 splanchnic nerve stimulation results in transient 

 arterial hypertension (141). The mechanisms of these 

 reactions have not been subjected to detailed analysis 

 and it is impossible at present to evaluate them in 

 terms of venous return, peripheral vascular resistances, 

 and local splanchnic and hepatic hemodynamics. 

 The splanchnic vasculature also undergoes changes 

 that appear to arise reflexly from other parts of the 

 cardiovascular system, such as the carotid sinuses and 

 great veins, but the usual difficulties in interpretation 

 arise in connection with widespread and simultaneous 

 circulatory adjustments in the remainder of the body. 

 Perhaps the venoconstriction with increased carotid 

 sinus tension and the venodilation during a fall in 

 carotid sinus tension, or during distension of the in- 

 ferior vena cava noted by Alexander (4, 5) in isolated 

 innervated segments of the mesenteric veins, may be 

 regarded as reasonably clear-cut evidence of reflex 

 action, but even here uncertainty must remain re- 

 garding myogenic and humoral factors. Since the 

 venodilator response is abolished by section of both 

 vagi, these reservations seem ill-founded and a reflex 

 with an afferent pathway via the vagal trunks may be 

 postulated. Certainly afferent pathways from other 

 parts of the body seem to be capable of activating 

 visceral neural outflow and visceral vascular responses 

 to peripheral stimulation. Heating or chilling the 

 skin, a rise of pressure in the carotid sinus, distention 

 of the inferior vena cava, and stimulation of the 

 central end of the severed sciatic nerve have all been 

 shown to elicit changes in the splanchnic vasculature 

 (4, 5, 132). The blushing or blanching of the gastric 

 or rectal mucosa during emotional responses (156, 

 192) also suggests that cortical activity, mediated by 

 pathways that begin in the cortical motor projection 

 of the splanchnic autonomic system, may affect the 

 splanchnic and hepatic circulation. 



Neurohumoral Determinants 



Confusion regarding the neural determinants of 

 flows and volumes within the splanchnic vessels is 

 inevitable not only because responses are so complex 

 but also because so little is known about the structure 

 and function of the neurovascular units. Several types 

 of nerve endings and receptors in vascular smooth 

 muscle have been postulated to account for the varied 

 responses to neural stimulation, to neurohumoral 

 transmitters, and to blocking agents, but too little is 

 known with assurance to permit the formulation of a 

 fully satisfactory explanation. Recent work (161) 

 suggests that norepinephrine alone is released from 

 the nerve endings in the splanchnic vessels, and that 

 receptors (J3) responsive to circulatory epinephrine 

 are present in the mesenteric, splenic, and hepatic 

 vessels. Reserpine appears to be capable of releasing 

 norepinephrine from splanchnic nerves, whereas the 

 circulating amine, released by the adrenal medulla or 

 introduced extraneously, can replenish the depleted 

 store (69). Dopamine, the immediate precursor to 

 norepinephrine, accounts for more than 95 per cent of 

 the catecholamine demonstrable in the liver, jejunum, 

 and colon where it appears to occur to a large extent 

 in nonneural tissue (263). In the spleen and the 

 pancreas, norepinephrine and epinephrine are found 

 in approximately equal amounts as in adrenergic 

 nerves. The large local supply of dopamine may imply- 

 that it has an action of its own. Acetylcholine has been 

 found in large amounts in the spleens of some species 

 (100) in accord with some evidence for cholinergic 

 vasodilator receptors in the splenic vessels. The inter- 

 play of all these factors in any single neurovascular 

 reaction is extremely difficult to follow, especially in 

 view of differences in responsiveness, independent 

 myogenic reactivity, and innervation within what 

 Folkow (130) has referred to as the "series-coupled" 

 and "parallel-coupled circuits" of the hepatic and 

 splanchnic vasculature. Study of the pattern of re- 

 sponse to individual chemical agents may ultimately 

 clarify the mechanism of these responses and throw- 

 light upon the local and systemic role of the hormones 

 themselves. 



EPINEPHRINE AND NOREPINEPHRINE. To what extent 



the circulating catecholamines participate in vaso- 

 motor adjustments remains uncertain. Neural activity 

 appears to exert a profound and selective action, 

 effectively controlling splanchnic vasomotor function 

 without need for an adjuvant (79, 130). The total 

 range of control by direct sympathetic innervation is 



