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• W2063162308 abstract "We hypothesized that tumor necrosis factor-α (TNF-α) mimics endotoxin in attenuating endothelium-dependent vasodilation and smooth muscle constriction of rat renal arteries, and that tyrosine kinase is involved. Isolated rat renal arteries (n = 6 per group), pretreated for 2 h by genistein (4´,5,7-trihydroxyisoflavone, 10 μg/mL, a tyrosine kinase inhibitor) or vehicle, were exposed for 2 h to recombinant human (rh) TNF-α (100 ng/mL) or vehicle. rhTNF-α attenuated (P < 0.05) the constriction response to depolarizing 125 mM KCl (952.6 ± 125.3 mg/mm vs. 1191.4 ± 136.8 mg/mm in rhTNF-α-exposed and control segments, respectively), but did not affect the constriction response to norepinephrine (NE, 0.01–10 μM). Genistein did not affect the constriction response to KCl. The concentration-response relation to NE in genistein-pretreated control segments showed (P < 0.05) a rightward shift, while the maximum constriction was not affected. Genistein did not prevent a reduction (P < 0.05) by rhTNF-α in the maximum response to NE (721.7 ± 42.4 mg/mm vs. 999.8 ± 84.4 mg/mm in controls). The endothelium-dependent relaxation induced by (acetyl choline) ACh (0.001–1.0 μM) was attenuated (P < 0.05) by rhTNF-α (39.4% ± 6.7% and 77.4% ± 10.0% in rhTNF-α-exposed and control segments, respectively). The reduction (P < 0.05) in maximum ACh-induced relaxation after exposure to rhTNF-α was not affected by genistein (44.6% ± 3.4% and 70.8% × 2.2% in genistein-pretreated rhTNF-α-exposed and control segments, respectively). Hence, the attenuated endothelium-dependent relaxation and smooth muscle constriction of rat renal arteries following short-term rhTNF-α exposure, mimicking the effect of endotoxin, does not involve the activity of tyrosine kinase. The latter may be involved in pharmacomechanical coupling, by increasing Ca2+ sensitivity, but less in the electromechanical coupling of smooth muscle constriction." @default.
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• W2063162308 date "2002-05-01" @default.
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• W2063162308 title "Tumor Necrosis Factor-?? Impairs Endothelium-Dependent Relaxation of Rat Renal Arteries, Independent of Tyrosine Kinase" @default.
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• W2063162308 doi "https://doi.org/10.1097/00024382-200205000-00009" @default.
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