Original Report: Laboratory Investigation

The Selective TP Receptor Antagonist, S18886 (Terutroban), Attenuates Renal Damage in the Double Transgenic Rat Model of Hypertension
Katarína ebeková^a, Anika Ramuscak^b, Peter Boor^a, August Heidland^c, Kerstin Amann<sup>b

a</sup>Slovak Medical University, Bratislava, Slovakia;
^bUniversity of Erlangen-Nürnberg, Erlangen, and
^cUniversity of Würzburg, Würzburg, Germany

Address of Corresponding Author

Am J Nephrol 2008;28:47-53 (DOI: 10.1159/000108760)

  Key Words

• Renin-angiotensin system
• Hypertension
• Thromboxane
• Glomerulosclerosis
• Tubulointerstitial damage
• Proteinuria

  Abstract

Background/Aims: Thromboxane receptors play a decisive role in the renovascular actions of angiotensin II. We studied the efficacy of the selective thromboxane receptor antagonist, S18886, in the retardation of renal damage in the double transgenic rats (dTGR), harboring human renin and angiotensinogen genes. Methods: dTGR were gavaged daily with either S18886 (30 mg/kg/day, n = 12), or placebo (dTGR-Plac, tap water, n = 14) for 3 weeks. Matched Sprague-Dawley rats (n = 10) served as controls. Results: The dTGR-Plac had higher systolic blood pressure (1.7-fold) than controls, and developed profound renal damage with significantly higher proteinuria (6.9-fold), polyuria (2.3-fold), index of glomerulosclerosis (+58%), and tubulointerstitial (+47%) and vascular damage scores (+19%). Creatinine concentration and the mesangiolysis index remained unchanged. In dTGR, S18886 slightly lowered the blood pressure (162 ± 15 vs. 149 ± 13 mm Hg, not significant) and improved proteinuria (558 ± 218 vs. 136 ± 71 mg/µmol creatinine, p < 0.01), polyuria and renal morphology (glomerulosclerosis index: 0.79 ± 0.05 vs. 0.66 ± 0.13, p < 0.01; tubulointerstitial damage index: 1.82 ± 0.22 vs. 1.49 ± 0.27, p < 0.05; mesangiolysis index: 1.31 ± 0.18 vs. 0.36 ± 0.09, p < 0.01). Vascular damage score and plasma creatinine were not influenced. S18886 did not alter measured markers of oxidative stress. Conclusion: The data present the first evidence that thromboxane receptor inhibition ameliorates angiotensin II-induced nephropathy.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Katarína ebeková, MD, PhD
Slovak Medical University, Limbová 14
SK-83303 Bratislava (Slovakia)
Tel. +421 2 5936 9431, Fax +421 2 5936 9170
E-Mail katarina.sebekova@szu.sk

  Article Information

Accepted: May 30, 2007
Accepted: July 25, 2007
Published online: September 21, 2007
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 2, Number of References : 31