Hypertension with poor glycemic control in iddm is not dependent on a decrease in insulin perse

We have reported that poor glycémie control very early in insulin-dependent diabetes mellitus (IDDM) is closely associated with a significant increase in blood pressure. The goal of this study was to determine the relative importance of elevated blood glucose versus low insulin in mediating the rise in blood pressure. Sprague Dawley rats (n=8) were instrumented with artery and vein catheters and mean arterial pressure (MAP) was measured 24 hours/day. Following a pre-conttol period, streptozotocin (70 mg/kg) was administered iv. A 4 U/day iv. infusion of regular insulin was begun in all rats the following day, and the dose was titrated individually over the next 6 days to maintain good glycémie control. After this 7-day period, the insulin dose was lowered in 3 rats (LI) for a 4-day diabetic period. In the other 5 rats (HG) the insulin dose was not changed and the rats were given 4.3 g glucose/day iv. for 4 days. Blood glucose increased to an average of 392+24 and 450±12 mg/dl in the LI and HG rats, respectively. MAP increased significantly from 99±6 to 108+5 mmHg in LI rats and from 103±5 to 113+5 in HG rats, with no differences between groups. Sodium excretion also increased, from 2.5+0.3 to 3.5+0.2 mEq/day in LI rats and from 2.6+0.2 to 3.6+0.1 mEq/day in HG rats, and was associated with a significant rise in hematocrit, from 38+1 to 42±1 % (LI) and 37+1 to 43+1 % (HG). Thus, the increase in blood glucose yielded similar renal and systemic changes whether insulin activity was decreased (LI) or maintained at normal levels (HG), suggesting that the hypertension in early, poorly controlled IDDM is not dependent on a decrease in insulin per se. (Supported by HL 51971, the American Heart Association, and the AHA MS Affiliate).