Nitric oxide inhibits norepinephrine-induced hepatic vascular responses but potentiates hepatic glucose output
Loading...
Date
2000-01-31
Authors
Ming, Z
Han, C
Lautt, WW
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
We previously reported that sympathetic nerve-induced vasoconstriction in the intestine resulted in shear stress induced release of nitric oxide (NO) that led to presynaptic inhibition of transmitter release. In contrast, studies in the liver suggested a postsynaptic inhibition of vascular responses, thus leading to the hypothesis tested here that maintained catecholamine release in the liver would result in maintained metabolic catecholamine action in the face of inhibition of vascular responses. In rats, norepinephrine (NE) induced elevations in arterial glucose content were inhibited by NO synthase antagonism (N-omega-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg, intraportal) but potentiated by NO donor administration (3-morpholinosydnonimine (SIN-1), 0.2 mg/kg, intraportal). The potentiated effect of SIN-1 was abolished by indomethacin (7.5 mg/kg, intraportal). To confirm the hepatic site of metabolic effect, cats were used so that blood flow and hepatic glucose balance could be determined. SIN-1 potentiated NE-induced glucose output from the liver from 5.0 +/- 0.4 to 7.2 +/- 0.6 mg.min(-1.)kg(-1). The potentiation was blocked by methylene blue, a guanylate cyclase inhibitor. Contrary to the glucose response, L-NAME potentiated but SIN-1 attenuated NE-induced portal vasoconstriction. Thus NO is shown to produce differential modulation of vascular and metabolic effects of NE. Vasoconstriction of the hepatic vasculature is inhibited by NO, whereas the glycogenolytic response to NE is potentiated, responses that are probably mediated by prostaglandin.
Description
Keywords
prostaglandin, glucose, portal vasculature, N-omega-nitro-L-arginine methyl ester, 3-morpholinosydnonimine, PERFUSED-RAT-LIVER, ENDOTHELIAL-CELLS, HEPATOCYTES, GLYCOGENOLYSIS, MODULATION, INSULIN, METABOLISM, RESISTANCE, DECREASE, SHOCK
Citation
0008-4212; CAN J PHYSIOL PHARMACOL, JAN 2000, vol. 78, no. 1, p.36 to 44.