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Am J Physiol Heart Circ Physiol 290: H209-H216, 2006. First published August 19, 2005; doi:10.1152/ajpheart.00208.2005
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Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats

Katari A. Carello,1 Steven E. Whitesall,1 Mary C. Lloyd,1 Scott S. Billecke,1 and Louis G. D'Alecy1,2,3

Departments of 1Molecular and Integrative Physiology and 2Surgery (Vascular), University of Michigan Medical School, Ann Arbor, Michigan; and 3Department of Surgery, William Beaumont Hospital, Royal Oak, Michigan

Submitted 3 March 2005 ; accepted in final form 15 August 2005

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 sham operation, bilateral nephrectomy (NPX), ureteral ligation, or ureteral section under isoflurane anesthesia. Tail-snip blood samples (250 µl) were taken before and at 6- or 12-h intervals for 72 h after operation. Plasma clearance was assessed in intact and NPX rats. High-performance liquid chromatography determined SDMA and ADMA concentrations. Sodium, potassium, creatinine, blood urea nitrogen (BUN), and body weight were also measured. Forty-eight hours after NPX, SDMA increased 25 times (0.23 ± 0.03 to 5.68 ± 0.30 µM), whereas ADMA decreased (1.17 ± 0.08 to 0.73 ± 0.08 µM) by 38%. Creatinine and BUN increased, paralleling SDMA. Sham-operated 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 that acute total NPX either reduced systemic ADMA formation and/or systemic hydrolysis of ADMA increased 48-h post-NPX. However, plasma clearance of ADMA appeared unchanged 48 h after NPX. 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.

nitric oxide synthase inhibitor; dimethylarginine dimethylaminohydrolase; source of asymmetrical dimethylarginine


Address for reprint requests and other correspondence: L. G. D'Alecy, Dept. of Molecular and Integrative Physiology, Univ. of Michigan Medical School, 7708 Medical Sciences Bldg. II, 1301 E. Catherine, Ann Arbor, MI 48109-0622 (e-mail:lgdalecy{at}umich.edu)




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