MECHANISMS OF INSULIN ACTION ON SYMPATHETIC-NERVE ACTIVITY

Insulin resistance and hyperinsulinemia may contribute to the developm ent of arterial hypertension. Although insulin may elevate arterial pr essure, in part, through activation of the sympathetic nervous system, the sites and mechanisms of insulin-induced sympathetic excitation re main uncertain. While sympathoexcitation during insulin may be mediate d by the baroreflex, or by modulation of norepinephrine release from s ympathetic nerve endings, it has been shown repeatedly that insulin in creases sympathetic outflow by actions on the central nervous system. Previous studies employing norepinephrine turnover have suggested that insulin causes sympathoexcitation by acting in the hypothalamus. Rece nt experiments from our laboratory involving direct measurements of re gional sympathetic nerve activity have provided further evidence that insulin acts in the central nervous system. For example, administratio n of insulin into the third cerebralventricle increased lumbar but not renal or adrenal sympathetic nerve activity in normotensive rats. Int erestingly, this pattern of regional sympathetic nerve responses to ce ntral neural administration of insulin is similar to that seen with sy stemic administration of insulin. Further, lesions of the anteroventra l third ventricle hypothalamic (AV3V) region abolished increases in sy mpathetic activity to systemic administration of insulin with euglycem ic clamp, suggesting that AV3V-related structures are critical for ins ulin-induced elevations in sympathetic outflow.