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Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice.

Publication ,  Journal Article
Boffa, J-J; Just, A; Coffman, TM; Arendshorst, WJ
Published in: J Am Soc Nephrol
September 2004

Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2 (TxA(2)) may mediate decreases of renal blood flow (RBF) and/or GFR associated with LPS-induced sepsis. This study tested whether TxA(2) receptor blockade, with the use of TxA(2) receptor knockout (TP-KO) mice or a selective TP receptor antagonist (SQ29,548), would alleviate LPS-induced renal vasoconstriction and ARF. Under basal conditions, anesthetized TP-KO mice displayed a lower mean arterial pressure than wild-type (WT) mice (102 versus 94 mmHg; P < 0.05). RBF, renal vascular resistance (RVR), GFR, and urine flow did not differ among groups under basal conditions, suggesting little tonic influence of TxA(2) on renal TP receptors in health. In endotoxemic WT mice, 14 h after LPS (Escherichia coli LPS 8.5 mg/kg intraperitoneally), mean arterial pressure was reduced to 85 mmHg (P < 0.001), as were RBF (5.0 versus 9.3 ml/min per g kidney wt; P < 0.001) and GFR (0.38 versus 1.03 ml/min per g kidney wt; P < 0.001). Heart rate and RVR (71 versus 47 mmHg/ml per min; P < 0.05) increased. The decreases in RBF and GFR after LPS were attenuated in TP-KO mice versus WT mice (both P < 0.05). In both TP-KO and TP antagonist-treated mice, RVR remained stable in response to LPS versus WT mice that did not receive LPS. Delayed TP-antagonist treatment (12 h after LPS injection) ameliorated RBF and RVR but did not restore GFR. In other WT animals, TP-antagonist treatment for 2 h before intravenous LPS abolished the early renal vasoconstriction and alleviated the decrease in GFR. These results demonstrate that renal vasoconstriction during endotoxemic shock induced by LPS is mediated by TP receptors as indicated by pharmacologic blockade and genetic disruption of TP receptors.

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Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

September 2004

Volume

15

Issue

9

Start / End Page

2358 / 2365

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Urology & Nephrology
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Mice
  • Male
  • Kidney
  • Endotoxemia
  • Animals
  • Acute Kidney Injury
  • 3202 Clinical sciences
 

Citation

APA
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ICMJE
MLA
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Boffa, J.-J., Just, A., Coffman, T. M., & Arendshorst, W. J. (2004). Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice. J Am Soc Nephrol, 15(9), 2358–2365. https://doi.org/10.1097/01.ASN.0000136300.72480.86
Boffa, Jean-Jacques, Armin Just, Thomas M. Coffman, and William J. Arendshorst. “Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice.J Am Soc Nephrol 15, no. 9 (September 2004): 2358–65. https://doi.org/10.1097/01.ASN.0000136300.72480.86.
Boffa J-J, Just A, Coffman TM, Arendshorst WJ. Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice. J Am Soc Nephrol. 2004 Sep;15(9):2358–65.
Boffa, Jean-Jacques, et al. “Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice.J Am Soc Nephrol, vol. 15, no. 9, Sept. 2004, pp. 2358–65. Pubmed, doi:10.1097/01.ASN.0000136300.72480.86.
Boffa J-J, Just A, Coffman TM, Arendshorst WJ. Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice. J Am Soc Nephrol. 2004 Sep;15(9):2358–2365.

Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

September 2004

Volume

15

Issue

9

Start / End Page

2358 / 2365

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Urology & Nephrology
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Mice
  • Male
  • Kidney
  • Endotoxemia
  • Animals
  • Acute Kidney Injury
  • 3202 Clinical sciences