Glomerular actions of a free radical-generated novel prostaglandin, 8-epi-prostaglandin F2 alpha, in the rat. Evidence for interaction with thromboxane A2 receptors.

Takahashi K, Nammour TM, Fukunaga M, Ebert J, Morrow JD, Roberts LJ, Hoover RL, Badr KF
J Clin Invest. 1992 90 (1): 136-41

PMID: 1386085 · PMCID: PMC443072 · DOI:10.1172/JCI115826

8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) 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 micrograms/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 microgram/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-PGF2 alpha 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-PGF2 alpha to RASM or isolated glomeruli was not associated with stimulation of arachidonate cyclooxygenase products. Therefore, 8-epi-PGF2 alpha 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.

MeSH Terms (17)

Animals Blood Pressure Bridged Bicyclo Compounds, Heterocyclic Dinoprost Fatty Acids, Unsaturated Free Radicals Glomerular Filtration Rate Hematocrit Hydrazines Kidney Glomerulus Male Rats Rats, Inbred Strains Receptors, Prostaglandin Receptors, Thromboxane Renal Circulation Thromboxane A2

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