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 activated during stress. Hepatic norepinephrine spillover (HNESO) was measured in halothane-anesthetized dogs before, during and after glucopenia, hypoxia and hemorrhage. HNESO increased during 2-deoxyglucose (2-DG, 600 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 HNESO increased by 84 +/- 22 ng/min (p < 0.01) during hemorrhage (mean arterial blood pressure = 40 +/- 1 mmHg), suggesting activation of hepatic sympathetic nerves during all three stresses. To validate the use of HNESO as an index of hepatic sympathetic nerve activity, we repeated the stresses of hypoxia and hemorrhage in dogs following chemical sympathetic denervation of the liver induced by prior intraportal 6-hydroxy-dopamine infusion. Hepatic denervation reduced the HNESO responses to hypoxia and hemorrhage by more than 90%. In addition to hepatic neural responses to stress, the sympathetic responses of the adrenal medulla and of systemic sympathetic nerves were monitored using changes in the arterial concentration of epinephrine and norepinephrine, respectively. Arterial epinephrine and norepinephrine increased by varying degrees 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 norepinephrine responses to hypoxia and hemorrhage were modestly reduced in hepatically sympathectomized animals, suggesting a small hepatic contribution to the elevated arterial level of norepinephrine during these stresses. We conclude that: (1) the stresses of glucopenia, hypoxia and hemorrhage activate the sympathetic nerves of the liver and (2) HNESO is a valid index of hepatic sympathetic nerve activity. Finally, we speculate that such activation may influence liver function.