Fenoldopam inhibits nuclear translocation of nuclear factor kappa B in a rat model of surgical ischemic acute renal failure

Journal of Cardiothoracic and Vascular Anesthesia
Natarajan AravindanAndrew D Shaw

Abstract

Vasoactive compounds are known to modulate gene transcription, including nuclear factor kappa B (NF-kappaB), in renal tissues, but the molecular effects of fenoldopam in this setting are not known. The authors used a rat model of surgical acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates ischemia/reperfusion (I/R)-induced NF-kappaB-mediated inflammation. Prospective, single-blind, randomized, controlled animal study. Academic Department of Anesthesiology laboratory. Twenty-four male Sprague-Dawley rats. Rats were anesthetized by intraperitoneal administration of 50 mg/kg of urethane and randomly allocated into 4 groups (n = 6 each): sham operation, sham operation with infusion of 0.1 microg/kg/min of fenoldopam, unilateral renal ischemia (1 hour, left renal artery cross-clamping) followed by 4 hours of reperfusion, and unilateral renal I/R with fenoldopam infusion. Kidney samples were used to measure NF-kappaB DNA-binding activity with an electrophoretic mobility shift assay. NF-kappaB signaling-dependent gene transcription was assessed with microarray analysis, and validated with reverse transcriptase polymerase chain reaction (RT-PCR). Expression of insulin-like growth factor-1 and nitric oxide synt...Continue Reading

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