Fenoldopam improves corticomedullary oxygen delivery and attenuates angiogenesis gene expression in acute ischemic renal injury.
OBJECTIVE
Vasoactive compounds are known to affect intrarenal hemodynamics and gene transcription, but specific effects of fenoldopam in the setting of acute renal ischemia are not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that fenoldopam improves corticomedullary tissue oxygen tension (PtO2) and attenuates angiogenesis gene expression in acute renal ischemia.


METHODS
Rats anesthetized with 50 mg/kg urethane were divided into 4 groups (n = 6 each): (1) sham with infusion of 0.9% saline; (2) sham with infusion of 0.1 microg x kg(-1) x min(-1) fenoldopam; (3) unilateral renal ischemia followed by 6 h of reperfusion with saline, and (4) ischemia/reperfusion with fenoldopam. Renal artery blood flow (RBF), renal cortical perfusion (RCP), and PtO2 were recorded throughout. Total RNA from left kidneys was used to probe microarrays. Gene expression was measured as percent positive control (GAPDH) and confirmed using RT-PCR.


RESULTS
Fenoldopam significantly increased RBF (p < 0.05), RCP (p < 0.01) and PtO2 (p <0.01) in both non-ischemic and post-ischemic kidneys. Fenoldopam attenuated 11 of the 13 ischemia-induced genes and 44 of 78 ischemia-suppressed genes. This attenuation was statistically significant (p < 0.05) for five genes.


CONCLUSIONS
Data from this rat model of ischemic nephropathy suggest that fenoldopam improves intrarenal hemodynamics and attenuates ischemia-related changes in angiogenesis gene expression.
Aravindan
Natarajan
N
Division of Anesthesiology and Critical Care, University of Texas MD Anderson Cancer Center, Houston, TX, USA. narvind@ouhsc.edu
Samuels
Joshua
J
Riedel
Bernhard
B
Shaw
Andrew
A
D000208:Acute Disease; D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D018818:Fenoldopam / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control
D043925:Angiogenesis Inducing Agents; D018818:Fenoldopam