Effect of fenoldopam on ischemia/reperfusion-induced apoptosis.
Recently we demonstrated the effect of fenoldopam on ischemia/reperfusion (I/R) induced NFkappaB mediated pro-inflammatory signal transduction. However, the effect of fenoldopam on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam attenuates I/R-induced apoptosis. Sprague-Dawley rats were anesthetized by intraperitoneal administration of 50 mg/kg urethane and randomly allocated into 4 groups (n=6 each): (1) sham-operated, (2) sham operation with infusion of 0.1 microg/kg/min fenoldopam, (3) unilateral renal ischemia followed by 4 h of reperfusion, and (4) I/R with fenoldopam infusion. Kidney samples were fixed and paraffin-embedded to measure apoptosis. Data were compared between groups using ANOVA with Bonferroni correction. RNA was extracted from each left kidney to probe cDNA microarray and measure gene expression as percent of positive control. Compared to the control group, I/R significantly (P < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that IR induced 73 apoptosis-related genes. Treatment with fenoldopam significantly reduced (P < 0.001) I/R-induced apoptosis both in the cortex and medulla and attenuated all 73 I/R-induced apoptosis-related genes. Data from this rat model of ischemic nephropathy suggest that fenoldopam may attenuate I/R-induced apoptosis and apoptosis-related gene transcription.
Aravindan
Natarajan
N
Division of Anesthesiology and Critical Care, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. naravind@mdanderson.org
Cata
Juan P
JP
Dougherty
Patrick M
PM
Shaw
Andrew D
AD
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000502:physiology; D018818:Fenoldopam / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014158:Transcription, Genetic / Q000187:drug effects
D000959:Antihypertensive Agents; D018818:Fenoldopam