Hindlimb blood flow control very early in insulin-dependent diabetes mellitus

Study of the direct effect of poor glycemic control on skeletal muscle blood flow has been hampered by potential confounding influences from: anesthesia, acute flow measurements, prolonged hyperglycemia prior to study, and from the diabetes-inducing agent itself. We addressed these concerns by studying hindlimb flow in 3 rats chronically instrumented with a venous catheter, a Transonic flow probe on the abdominal aorta at the iliac bifurcation, and an aortic catheter inserted through the aortic wall just superior to the flow probe. Hindlimb flow was recorded 24 h/day. 12-15 hours after administration of streptozotocin (STZ), a 24 h/day i.v. insulin-replacement (IR) infusion was begun in each rat and individually titrated to restore normal glycemia. 5 days later, the insulin dose was lowered to induce diabetes (D), with an average blood glucose of 434+15 mg/dl for a 6-day period. In addition, the acute flow responses to acetylcholinc and nitroprusside (ACh and NP; each at 1 and 10 μg/min, 20 min/dose, 90 μl/min via the aortic catheter) were measured preSTZ (C), on day 4 of IR, days 2 and 6 of D, and day 6 of the IR recovery period. 24-hr hindlimb flow averaged 25+5 ml/min during C and 94±8% of C on IR5. Flow decreased steadily during D to 33±3% of C on D6 and rose steadily during the recovery IR to 117±10% of C by IR6. Flow increased 152±23 and 237±11% of control with ACh and 132±3 and 146±4% of control with SNP at the two doses during C. The responses were not different on any day except for enhanced responses to both agents on D6. Thus, early and reversible decreases in skeletal muscle flow as well as enhanced responsiveness to nitric oxide accompany poor glycemic control in IDDM rats.