To. Mundinger et al., ACTIVATION OF HEPATIC SYMPATHETIC-NERVES DURING HYPOXIC, HYPOTENSIVE AND GLUCOPENIC STRESS, Journal of the autonomic nervous system, 63(3), 1997, pp. 153-160
To investigate the potential for neural regulation of liver function,
we sought to determine whether hepatic sympathetic nerves are activate
d during stress. Hepatic norepinephrine spillover (HNESO) was measured
in halothane-anesthetized dogs before, during and after glucopenia, h
ypoxia and hemorrhage. HNESO increased during 2-deoxyglucose (2-DG, 60
0 mg/kg plus 13.5 mg/kg/min, IV)-induced glucopenia from a baseline of
9 +/- 3 ng/min to 83 +/- 24 ng/min (Delta = +74 +/- 23 ng/min, p < 0.
01). During hypoxia (partial pressure of oxygen in arterial blood = 23
+/- 2 mmHg), HNESO increased by 142 +/- 47 ng/min (p < 0.025), and HN
ESO increased by 84 +/- 22 ng/min (p < 0.01) during hemorrhage (mean a
rterial blood pressure = 40 +/- 1 mmHg), suggesting activation of hepa
tic sympathetic nerves during all three stresses. To validate the use
of HNESO as an index of hepatic sympathetic nerve activity, we repeate
d the stresses of hypoxia and hemorrhage in dogs following chemical sy
mpathetic denervation of the liver induced by prior intraportal 6-hydr
oxy dopamine infusion. Hepatic denervation reduced the HNESO responses
to hypoxia and hemorrhage by more than 90%. In addition to hepatic ne
ural responses to stress, the sympathetic responses of the adrenal med
ulla and of systemic sympathetic nerves were monitored using changes i
n the arterial concentration of epinephrine and norepinephrine, respec
tively. Arterial epinephrine and norepinephrine increased by varying d
egrees during all three stresses, suggesting general sympatho-adrenal
activation. As expected, 6-hydroxydopamine pretreatment did not alter
the epinephrine response to hypoxia or hemorrhage. The arterial norepi
nephrine responses to hypoxia and hemorrhage were modestly reduced in
hepatically sympathectomized animals, suggesting a small hepatic contr
ibution to the elevated arterial level of norepinephrine during these
stresses. We conclude that: (1) the stresses of glucopenia, hypoxia an
d hemorrhage activate the sympathetic nerves of the liver and (2) HNES
O is a valid index of hepatic sympathetic nerve activity. Finally, we
speculate that such activation may influence liver function.