Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat

Kihito Takahashi, George F. Schreiner, Kouwa Yamashita, Brian W. Christman, Ian Blair, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

While much is known regarding acute nephrotoxic serum (NTS)-induced glomerular injury, the glomerular dynamics and pathophysiologic mediators of the more relevant chronic autologous phase remain poorly defined. Studies were performed in rats 14 d after injection of rabbit serum (n = 6), NTS in the absence (n = 6), or presence, of a cyclooxygenase inhibitor, ibuprofen (n = 6) or a thromboxane A2 (TxA2) receptor antagonist, L-670,596 (n = 5). A mesangial macrophage/ monocyte infiltrate was noted with equal intensity in all NTS-treated rats. Glomerular generation rates of prostaglandin (PG) E2, PGF2a, and TxA2 in nephritic kidneys were dramatically increased as compared to controls. 2 wk after NTS, there was an increase in glomerular plasma flow rate (SNPF), attainment of filtration pressure disequilibrium, and augmentation of net transcapillary hydraulic pressure difference (ΔP). Glomerular filtration rate (GFR), however, was reduced, due to a marked fall in the glomerular capillary ultrafiltration coefficient (Kf). Cyclooxygenase inhibition resulted in normalization of glomerular eicosanoid generation rates, amelioration of proteinuria, afferent vasoconstriction, and normalization of SNPF, ΔP, Kf, and GFR. Selective antagonism of TxA2 also led to preservation of Kf, but was without effect on SNPF, thereby leading to elevated values for GFR. Thus, in contrast to the pathophysiologic role of arachidonate-lipoxygenase products in the early heterologous phase, PG-mediated vasodilatation and TxA2-induced reductions in Kf and GFR underlie glomerular functional changes during autologous mesangioproliferative glomerulonephritis. (J. Clin. Invest. 1990. 85:1974-1982.

Original languageEnglish (US)
Pages (from-to)1974-1982
Number of pages9
JournalJournal of Clinical Investigation
Volume85
Issue number6
StatePublished - Jun 1990
Externally publishedYes

Keywords

  • Autologous phase
  • Glomerular hemodynamics
  • Glomerulonephritis
  • Prostaglandin e
  • Thromboxane

ASJC Scopus subject areas

  • Medicine(all)

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    Takahashi, K., Schreiner, G. F., Yamashita, K., Christman, B. W., Blair, I., & Badr, K. F. (1990). Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat. Journal of Clinical Investigation, 85(6), 1974-1982.