Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2α, in the rat: Evidence for interaction with thromboxane A2 receptors

Kihito Takahashi, Tarek M. Nammour, Megumu Fukunaga, Joan Ebert, Jason D. Morrow, L. Jackson Roberts, Richard L. Hoover, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

8-epi-prostaglandin F (8-cpi-PGF) and related compounds are novel prostanoid produced by a noncyclooxygenase mechanism involving lipid peroxidation. Renal ischemia-reperfusion injury increased urinary excretion of these compounds by 300% over baseline level. Intrarenal arterial infusion at 0.5, 1, and 2 μg/kg per min induced dose-dependent reductions in glomerular filtration rate (GFR) and renal plasma flow, with renal function ceasing at the highest dose. Micropuncture measurements (0.5 μg/kg per min) revealed a predominant increase in afferent resistance, resulting in a decrease in transcapillary hydraulic pressure difference, and leading to reductions in single nephron GFR and plasma flow. These changes were completely abolished or reversed by a TxA2 receptor antagonist, SQ 29,548. Competitive radioligand binding studies demonstrated that 8-epi-PGF is a potent competitor for [3H]SQ 29,548 binding to rat renal arterial smooth muscle cells (RASM) in culture. Furthermore, addition of 8-epi-PGF to RASM or isolated glomeruli was not associated with stimulation of arachidonate cyclooxygenase products. Therefore, 8-epi-PGF is a potent preglomerular vasoconstrictor acting principally through TxA2 receptor activation. These findings may explain, in part, the beneficial effects of antioxidant therapy and TxA2 antagonism observed in numerous models of renal injury induced by lipid peroxidation.

Original languageEnglish (US)
Pages (from-to)136-141
Number of pages6
JournalJournal of Clinical Investigation
Volume90
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

Prostaglandin H2 Receptors Thromboxane A2
Dinoprost
Free Radicals
Prostaglandins
Kidney
Glomerular Filtration Rate
Lipid Peroxidation
Smooth Muscle Myocytes
Renal Plasma Flow
Competitive Binding
Nephrons
Vasoconstrictor Agents
Prostaglandin-Endoperoxide Synthases
Reperfusion Injury
Punctures
Cell Culture Techniques
Antioxidants
Pressure
Wounds and Injuries

Keywords

  • Free radicals
  • Glomerulonephritis
  • Prostaglandins
  • Renal blood flow
  • Thromboxane

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Takahashi, K., Nammour, T. M., Fukunaga, M., Ebert, J., Morrow, J. D., Roberts, L. J., ... Badr, K. F. (1992). Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2α, in the rat: Evidence for interaction with thromboxane A2 receptors. Journal of Clinical Investigation, 90(1), 136-141.

Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2α, in the rat : Evidence for interaction with thromboxane A2 receptors. / Takahashi, Kihito; Nammour, Tarek M.; Fukunaga, Megumu; Ebert, Joan; Morrow, Jason D.; Roberts, L. Jackson; Hoover, Richard L.; Badr, Kamal F.

In: Journal of Clinical Investigation, Vol. 90, No. 1, 1992, p. 136-141.

Research output: Contribution to journalArticle

Takahashi, K, Nammour, TM, Fukunaga, M, Ebert, J, Morrow, JD, Roberts, LJ, Hoover, RL & Badr, KF 1992, 'Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2α, in the rat: Evidence for interaction with thromboxane A2 receptors', Journal of Clinical Investigation, vol. 90, no. 1, pp. 136-141.
Takahashi, Kihito ; Nammour, Tarek M. ; Fukunaga, Megumu ; Ebert, Joan ; Morrow, Jason D. ; Roberts, L. Jackson ; Hoover, Richard L. ; Badr, Kamal F. / Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2α, in the rat : Evidence for interaction with thromboxane A2 receptors. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 1. pp. 136-141.
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abstract = "8-epi-prostaglandin F2α (8-cpi-PGF2α) and related compounds are novel prostanoid produced by a noncyclooxygenase mechanism involving lipid peroxidation. Renal ischemia-reperfusion injury increased urinary excretion of these compounds by 300{\%} over baseline level. Intrarenal arterial infusion at 0.5, 1, and 2 μg/kg per min induced dose-dependent reductions in glomerular filtration rate (GFR) and renal plasma flow, with renal function ceasing at the highest dose. Micropuncture measurements (0.5 μg/kg per min) revealed a predominant increase in afferent resistance, resulting in a decrease in transcapillary hydraulic pressure difference, and leading to reductions in single nephron GFR and plasma flow. These changes were completely abolished or reversed by a TxA2 receptor antagonist, SQ 29,548. Competitive radioligand binding studies demonstrated that 8-epi-PGF2α is a potent competitor for [3H]SQ 29,548 binding to rat renal arterial smooth muscle cells (RASM) in culture. Furthermore, addition of 8-epi-PGF2α to RASM or isolated glomeruli was not associated with stimulation of arachidonate cyclooxygenase products. Therefore, 8-epi-PGF2α is a potent preglomerular vasoconstrictor acting principally through TxA2 receptor activation. These findings may explain, in part, the beneficial effects of antioxidant therapy and TxA2 antagonism observed in numerous models of renal injury induced by lipid peroxidation.",
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