ACTIVATION OF HEPATIC SYMPATHETIC-NERVES DURING HYPOXIC, HYPOTENSIVE AND GLUCOPENIC STRESS

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.