Sympathetic and vascular dysfunction in early experimental juvenile diabetes mellitus

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Abstract
Sympathetic autonomic neuropathy as well as small vessel angiopathy have separately been reported in diabetic patients. To evaluate these factors concomitantly in a model of severe, untreated diabetes (plasma glucose 500 mg/dl), alloxan was administered to rats at 4 wk of age and studied them 5 wk later. After seconal anesthesia (mean arterial pressure: control, 154 .+-. 5; diabetic, 126 .+-. 6 mm Hg; P < 0.001), the hindquarters of 10 diabetic (D) and 10 control (C) rats were perfused at constant flow per 100 g through the abdominal aorta with oxygenated Tyrode solution containing dextran. Efflux was from the ligated and severed inferior vena cava. To test the effect of a strong sympathetic stimulus producing reflex peripheral vasoconstriction, the cephalad portions of the rats were rapidly hemorrhaged. The increase in hindquarter perfusion pressure was markedly less in D (14 .+-. 3 mm Hg) than in C (56 .+-. 5 mm Hg) (P < 0.001). The hindquarter perfusion pressure of a 2nd control group was similar to that of D when hemorrhaged after section of the lumbar sympathetic chain (6 .+-. 1 mm Hg increase). To determine if peripheral sympathetic denervation occurred in D, the threshold response to norepinephrine in the perfusate was determined. The threshold was significantly lower in D than in C (0.17 .+-. 0.3 vs. 0.49 .+-. 0.04 .mu.g/ml, respectively, P < 0.001). The maximum vasoconstrictor capacity of the vasculature was tested with supramaximal doses of vasopressin and was significantly lower in D than in C (178 .+-. 17 vs. 262 .+-. 6 mm Hg, respectively, P < 0.001). A flow-pressure curve during maximal dilation, induced with papaverine, was significantly lower in D than in C (P < 0.001). Both sympathetic autonomic denervation and microvascular pathology apparently are present in alloxan-induced diabetes and can contribute to abnormalities in blood pressure control.