Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure

Author:

Evans Scott B.1,Wilkinson Charles W.2,Gronbeck Pam3,Bennett Jennifer L.1,Taborsky Gerald J.43,Figlewicz Dianne P.143

Affiliation:

1. Departments of Psychology and of

2. Geriatric Research, Education and Clinical Center, Department of Veterans Affairs, Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98195

3. Department of Veterans Affairs, Puget Sound Health Care System, Seattle 98108; and

4. Medicine, University of Washington, Seattle 98195;

Abstract

The anatomic 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 hypoglycemia-associated autonomic failure (HAAF), 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 indexes 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 ≥1 mm 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 hypothalamic-pituitary-adrenocortical axis response), but not in others (i.e., blunting the glucagon response).

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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