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Am J Physiol Heart Circ Physiol (August 19, 2005). doi:10.1152/ajpheart.00208.2005
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Submitted on March 3, 2005
Accepted on August 15, 2005

Asymmetrical dimethylarginine plasma clearance persists following acute total nephrectomy in rats

Katari A Carello1, Steven E Whitesall1, Mary C Lloyd1, Scott S Billecke1, and Louis G D'Alecy2*

1 Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA
2 Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Surgery (Vascular), University of Michigan Medical School, Ann Arbor, MI, USA; Surgery, William Beaumont Hospital, Royal Oak, MI, USA

* To whom correspondence should be addressed. E-mail: bilker{at}umich.edu.

Elevated plasma concentrations of symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA) are repeatedly associated with kidney failure. Both ADMA and SDMA can be excreted in urine. We tested whether renal excretion is necessary for acute/short-term maintenance of plasma ADMA and SDMA. Sprague-Dawley rats underwent either sham operation, bilateral nephrectomy, ureteral ligation, or ureteral section under isoflurane anesthesia. Tail-snip blood samples (250µL) were taken before and at 6 or 12h intervals for 72h after operation. Plasma clearance was assessed in intact and nephrectomized rats. High performance liquid chromatography determined SDMA and ADMA concentrations. Sodium, potassium, creatinine, blood urea nitrogen (BUN) and body weight were also measured. 48h following nephrectomy SDMA increased 25 times (0.23±0.03 to 5.68±0.30 µM) while ADMA decreased (1.17±0.08 to 0.73±0.08 µM) by 38%. Creatinine and BUN increased paralleling SDMA. Sham animals showed no significant changes. Increased SDMA confirms continuous systemic production of SDMA and its obligatory renal excretion much like creatinine. In contrast, decreased plasma ADMA suggests acute total nephrectomy either reduced systemic ADMA formation, and or, systemic hydrolysis of ADMA increased 48 hours post-nephrectomy. However, plasma clearance of ADMA appeared unchanged following nephrectomy. We conclude that renal excretory function is needed for SDMA elimination but not needed for acute/short-term ADMA elimination in that systemic hydrolysis is fully capable of clearing plasma ADMA.




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