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Departments of 1 Psychology and of 4 Medicine, University of Washington, Seattle 98195; 3 Department of Veterans Affairs, Puget Sound Health Care System, Seattle 98108; and 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
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).
paraventricular nucleus; hypothalamus; stress; rat; lidocaine
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