Direct evidence that an increase in aortic norepinephrine level in response to insulin-induced hypoglycemia is due to increased adrenal norepinephrine output

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Abstract
This study reports on the major source of circulating norepinephrine that is known to increase, progressively, during sustained hypoglycemia induced by intravenous insulin administration. Plasma concentrations of epinephrine, norepinephrine, and dopamine were simultaneously determined for adrenal venous and aortic blood in dogs anesthetized with sodium pentobarbital. The model used allowed us to perform a functional adrenalectomy (ADRX), while continuously monitoring the adrenal medullary secretory function. Under basal conditions, the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine were 0.169 ± 0.074, 0.067 ± 0.023, and 0.011 ± 0.003, respectively. Plasma concentrations (ng/mL) of aortic epinephrine, norepinephrine, and dopamine were 0.132 ± 0.047, 0.268 ± 0.034, and 0.034 ± 0.009. Following insulin injection (0.15 IU/kg, i.v.), the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine increased gradually (p < 0.05), reaching the values of 0.918 ± 0.200, 0.365 ± 0.058, and 0.034 ± 0.007 30 min after insulin administration. Similarly, aortic epinephrine, norepinephrine, and dopamine concentrations (ng/mL) increased significantly (p < 0.05) to 0.702 ± 0.144, 0.526 ± 0.093, and 0.066 ± 0.024. The aortic glucose concentration (mg/dL) was diminished from 81.8 ± 4.1 to 36.9 ± 3.4 (p < 0.01). After taking the blood sample at 30 min following insulin administration, ADRX was immediately performed. Five minutes after the onset of ADRX, the net output (μg/min) of adrenal epinephrine, norepinephrine, and dopamine increased further to 1.707 ± 0.374 (p < 0.05), 0.668 ± 0.139 (p < 0.05), and 0.052 ± 0.017. By contrast, aortic epinephrine, norepinephrine, and dopamine concentrations rapidly diminished (p < 0.05) to their initial control levels reaching 0.051 ± 0.014, 0.252 ± 0.023, and 0.031 ± 0.005 ng/mL, 5 min after ADRX. The present results indicate that during the early phase of insulin-induced hypoglycemia, circulating norepinephrine in aortic blood significantly increases due, primarily, to the enhanced adrenal norepinephrine output.Key words: insulin, plasma norepinephrine, adrenal catecholamines, functional adrenalectomy, hypoglycemia.

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