Increased renal production of angiotensin II and thromboxane B2 in conscious diabetic rats

Background: The mechanisms involved in development of cardiovascular complications associated with diabetes mellitus are not well elucidated. Among the vasoactive factors that may play a role in development of these complications are angiotensin II and thromboxane B-2 (TXB2). We hypothesized that diabetes increases renal production of TXB2 through stimulation of angiotensin type-1 receptor. Methods: We used a microdialysis technique to monitor changes in renal interstitial fluid (RIF) TXB2 in conscious streptozotocin-induced diabetes rat model. The RIF levels of angiotensin 11 and TXB2 were monitored before and during 6 weeks after development of diabetes and during treatment with the angiotensin type-1 receptor blocker valsartan at 10 mg/kg. Measurement of the urinary albumin excretion (UAE) was used to monitor the development and progression of diabetic nephropathy. Results: The UAE was 81.62 +/- 1.31 ng/min, 184.75 +/- 9.41 ng/min (P <.01), and 229.84 +/- 4.49 ng/min (P <.0001) at baseline, week 3, and week 6, respectively, after induction of diabetes. Basal levels of RIF angiotensin 11 were 4.28 +/- 0.02 Pg/mL and significantly increased to 6.24 +/- 0.31 pg/mL (P <.001) and 7.66 +/- 0.05 pg/mL (P <.001) at 3 and 6 weeks after development of diabetes. Similarly, basal RIF TXB2 was 197 +/- 27 pg/mL and increased to 488 80 pg/mL (P <.01) and 703 +/- 130 pg/mL (P <.01) at 3 and 6 weeks after development of diabetes. Valsartan caused further increase in RIF angiotensin II levels. In contrast, valsartan decreased RIF TXB2 levels at baseline to 85 11 pg/mL (P <.01), at 3 weeks to 141 +/- 17 pg/mL (P <.01), and at 6 weeks to 255 45 pg/mL (P <.01) after development of diabetes. Conclusions: These results demonstrate that diabetes mellitus is accompanied by increased renal production of angiotensin H and TXB2. The increase in TXB2 is mediated through stimulation of angiotensin type-1 receptor. (c) 2005 American Journal of Hypertension, Ltd.