Effect of Acute and Antecedent Hypoglycemia on Sympathetic Neural Activity and Catecholamine Responsiveness in Normal Rats
- William I. Sivitz12,
- Judith A. Herlein12,
- Donald A. Morgan13,
- Brian D. Fink12,
- Bradley G. Phillips4 and
- William G. Haynes13
- 1Internal Medicine, Divisions of
- 2Endocrinology and
- 3Cardiovascular Disease, and
- 4Pharmacology, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, Iowa
Adrenergic responsiveness to acute hypoglycemia is impaired after prior episodes of hypoglycemia. Although circulating epinephrine responses are blunted, associated alterations in adrenal sympathetic nerve activity (SNA) have not been reported. We examined adrenal nerve traffic in normal conscious rats exposed to acute insulin-induced hypoglycemia compared with insulin with (clamped) euglycemia. We also examined adrenal SNA and catecholamine responses to insulin-induced hypoglycemia in normal conscious rats after two antecedent episodes of hypoglycemia (days −2 and −1) compared with prior episodes of sham treatment. Acute insulin-induced hypoglycemia increased adrenal sympathetic nerve traffic compared with insulin administration with clamped euglycemia (165 ± 12 vs. 118 ± 21 spikes/s [P < 0.05]; or to 138 ± 8 vs. 114 ± 10% of baseline [P < 0.05]). In additional experiments, 2 days of antecedent hypoglycemia (days –2 and –1) compared with sham treatment significantly enhanced baseline adrenal SNA measured immediately before subsequent acute hypoglycemia on day 0 (180 ± 11 vs. 130 ± 12 spikes/s, respectively; P < 0.005) and during subsequent acute hypoglycemia (229 ± 17 vs. 171 ± 16 spikes/s; P < 0.05). However, antecedent hypoglycemia resulted in a nonsignificant reduction in hypoglycemic responsiveness of adrenal SNA when expressed as percent increase over baseline (127 ± 5% vs. 140 ± 14% of baseline). Antecedent hypoglycemia, compared with sham treatment, resulted in diminished epinephrine responsiveness to subsequent hypoglycemia. Norepinephrine responses to hypoglycemia were not significantly altered by antecedent hypoglycemia. In summary, prior hypoglycemia in normal rats increased adrenal sympathetic tone, but impaired epinephrine responsiveness to acute hypoglycemia. Hence, these data raise the intriguing possibility that increased sympathetic tone resulting from antecedent hypoglycemia downregulates subsequent epinephrine responsiveness to hypoglycemia. Alternatively, it is possible that the decrease in epinephrine responsiveness after antecedent hypoglycemia could be the result of reduced adrenal sympathetic nerve responsiveness.
Address correspondence and reprint requests to Dr. William Sivitz, Department of Internal Medicine, The University of Iowa Hospitals and Clinics, 3E-17 VA, Iowa City, IA 52246. E-mail:.
Received for publication 28 September 2000 and accepted in revised form 29 January 2001.
CV, coefficient of variation; MAP, mean arterial pressure; SNA, sympathetic nerve activity.