To determine the possibility that insulin and/or glucose may directly or indirectly modulate cardiovascular tone, we measured plasma glucose, arterial pressure and heart rate after the injection of insulin, 2-deoxyglucose (2-DG) and glucose into the femoral vein or into the lateral ventricles of Wistar rats. The systemic administration of insulin significantly decreased plasma glucose, while its intracerebroventricular (ICV) infusion had little effect on plasma glucose, although it resulted in a significant increase in plasma insulin. Both the peripheral and the ICV administration of insulin significantly decreased mean arterial pressure (MAP) and ICV insulin decreased heart rate. Injections of 2-deoxyglucose were used to help differentiate the effects of insulin from those of insulin-induced glucopenia. When infused systemically, 2-DG increased plasma glucose while ICV 2-DG had no significant effect on plasma glucose levels. When 2-DG was administered systemically, MAP and heart rate were increased slightly; however, they were significantly decreased when 2-DG was administered centrally. Both ICV and systemic administration of glucose increased plasma insulin even though ICV glucose did not significantly change the plasma glucose level. Both systemic and ICV administration of glucose significantly decreased MAP and heart rate. These results suggest that increasing the insulin and/or glucose concentration of the CNS environment may have a direct influence on autonomic outflow resulting in decreased MAP and heart rate. Central glucopenia induced by 2-DG suppressed sympathetic or increased parasympathetic outflow, while systemic glucopenia stimulated cardiovascular tone. Both systemic and central glucose administration suppressed the cardiovascular tone to a lesser extent than did administration of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)