Inactivation of the Paraventricular Nucleus of the Hypothalamus During Hypoglycemia Partially Simulates Hypoglycemia Associated Autonomic Failure

The anatomical connections of the paraventricular nucleus of the hypothalamus (PVN) are such that it is ideally situated to modulate and/or control autonomic responses to a variety of stressors, including hypoglycemia. In our experimental model of HAAF (hypoglycemiaassociated autonomic failure), a syndrome in which the counterregulatory response to hypoglycemia is partially compromised via unknown mechanisms, activation of the PVN is blunted (15). We hypothesized that this blunted PVN activation during HAAF may be sufficient to cause the impaired counterregulatory response. To test this hypothesis, we anesthetized the PVN with lidocaine during insulin-induced hypoglycemia in rats and measured counterregulatory hormone levels. PVN inactivation decreased indices of the sympathoadrenal response (plasma epinephrine and norepinephrine) and the hypothalamic/pituitary axis response (ACTH). Inactivation decreased the peak epinephrine response to hypoglycemia by almost half (-42 6% from control; p=0.04) and the peak norepinephrine response by 34 5% (p=0.01). The peak plasma ACTH levels attained were suppressed by 35 6% (p=0.02). Adrenal corticosterone and pancreatic glucagon responses were not impaired. This pattern of neuroendocrine response is unlike that previously seen with our HAAF model. Control infusions of lidocaine one millimeter or more anterior or posterior to the PVN did not simulate this neuroendocrine pattern. Thus, it appears that decreased PVN activation, as occurs with HAAF, may be involved in specific components of HAAF (i.e., blunting the sympathoadrenal and HPA response), but not in others (i.e. blunting the glucagon response).