Insulin-Like Growth Factor-I Decreases Sympathetic Nerve Activity: The Effect Is Modulated by Glycemic Status

Abstract

Insulin-like growth factor-l (IGF-I) has been demonstrated to exert metabolic as well as cardiovascular actions similar to those of insulin. In previous studies, we have demonstrated that IGF-I acts both peripherally and centrally to increase muscle and renal blood flow and to decrease mean arterial pressure (MAP). Insulin has similar cardiovascular actions and has also been demonstrated to increase sympathetic nerve activity that may or may not play a role in blood flow or arterial pressure regulation. In this study, we evaluated the effect of IGF-I on lumbar sympathetic nerve activity (LSNA) and renal sympathetic nerve activity (RSNA), and correlated these responses with MAP and glycemic status. Normal rats were anesthetized with chloralose/urethane, the femoral artery and vein were cannulated to monitor MAP or heart rate (HR), or for infusions. The lumbar sympathetic nerve or renal nerve was isolated and placed on electrodes embedded in silicone gel for recording of nerve activity. Cardiovascular and nerve activity responses to IGF-I were recorded using a Dasy Lab Acquisition System. The infusion of IGF-I resulted in a decrease in plasma glucose that was accompanied by a decrease in MAP and an increased LSNA. However, when IGF-I was infused and euglycemia was maintained by glucose replacement, the LSNA was decreased. Renal nerve recording demonstrated that the RSNA was decreased both when hypoglycemia was allowed to occur and when euglycemia was maintained. We conclude that IGF-I acts to decrease LSNA and RSNA, and that the activity of the LSNA to skeletal muscle can be increased by hypoglycemia.