Autonomic and endothelial dysfunction in experimental diabetes.

The effect of streptozotocin induced diabetes on autonomic regulation of heart rate and endothelial function was examined in Sprague-Dawley rats. Weanling rats (3-4 weeks of age) of either sex were randomly assigned to a non-diabetic (male 5, female 6) or diabetic (male 4, female 5). Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ, 100 mg/kg). Nondiabetic rats received an IP injection of saline. Eight weeks after injection, rats were chronically instrumented with a left jugular venous catheter and a left carotid arterial catheter. After recovery (5 days) cardiac sympathetic tonus, parasympathetic tonus and intrinsic heart rate were determined. On an alternative day, the pressor response to nitric oxide synthase inhibition (NOS-X) was determined in areflexic rats. Cardiac sympathetic tonus (72 +/- 13 vs. 41 +/- 7), parasympathetic tonus (-51 +/- 10 vs. -22 +/- 7), and intrinsic heart rate (368 +/- 6 vs. 292 +/- 9), were reduced in diabetic rats. Furthermore, diabetic rats had a smaller pressor response (A33 +/- 7 vs. A66 +/- 5) to NOS-X. These results document impaired autonomic control of heart rate and endothelial dysfunction in 8-week streptozotocin induced diabetic rats.