Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Hypertens. 2005 Apr;18(4 Pt 1):544-8.

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

Author information

  • 1Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.

Abstract

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 B2 (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 II 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 II 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 II and TXB2. The increase in TXB2 is mediated through stimulation of angiotensin type-1 receptor.

PMID:
15831366
DOI:
10.1016/j.amjhyper.2004.10.018
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Support Center