BACKGROUND: Recently, the potential importance of dimethylarginines as endogenously produced inhibitors of nitric oxide synthase has become clearer. Interestingly, elevated levels have been reported in patients with vascular disease, but especially in patients suffering end-stage renal disease. Although the kidney obviously seems to play a key role in the elimination of dimethylarginines, clear insight into the renal handling of these compounds is lacking. Thus, our aim was to investigate the renal extraction of dimethylarginines. METHODS: Plasma concentrations of dimethylarginines were determined in both arterial and renal venous blood in 20 fasting patients with normal renal function. Renal extraction was calculated as the arteriovenous concentration difference divided by the arterial concentration times 100%. RESULTS: A significant renal extraction was found for both dimethylarginines. Renal extraction was significantly higher for asymmetrical dimethylarginine (ADMA) when compared with symmetrical dimethylarginine (SDMA) (16.2 vs 10.5% respectively, P=0.001). In addition, arterial SDMA concentration, but not ADMA concentration, significantly correlated with arterial creatinine concentration. CONCLUSIONS: In healthy humans, the kidney contributes to the regulation of plasma levels of dimethylarginines, since both ADMA and SDMA were significantly extracted from the arterial supply. Interestingly, a higher renal extraction of ADMA was found when compared to SDMA extraction, which strongly suggests the presence of an additional catabolic pathway for ADMA in the kidney.
BACKGROUND: Recently, the potential importance of dimethylarginines as endogenously produced inhibitors of nitric oxide synthase has become clearer. Interestingly, elevated levels have been reported in patients with vascular disease, but especially in patients suffering end-stage renal disease. Although the kidney obviously seems to play a key role in the elimination of dimethylarginines, clear insight into the renal handling of these compounds is lacking. Thus, our aim was to investigate the renal extraction of dimethylarginines. METHODS: Plasma concentrations of dimethylarginines were determined in both arterial and renal venous blood in 20 fasting patients with normal renal function. Renal extraction was calculated as the arteriovenous concentration difference divided by the arterial concentration times 100%. RESULTS: A significant renal extraction was found for both dimethylarginines. Renal extraction was significantly higher for asymmetrical dimethylarginine (ADMA) when compared with symmetrical dimethylarginine (SDMA) (16.2 vs 10.5% respectively, P=0.001). In addition, arterial SDMA concentration, but not ADMA concentration, significantly correlated with arterial creatinine concentration. CONCLUSIONS: In healthy humans, the kidney contributes to the regulation of plasma levels of dimethylarginines, since both ADMA and SDMA were significantly extracted from the arterial supply. Interestingly, a higher renal extraction of ADMA was found when compared to SDMA extraction, which strongly suggests the presence of an additional catabolic pathway for ADMA in the kidney.
Authors: Rachel A Murphy; Steven Moore; Mary Playdon; Stephen Kritchevsky; Anne B Newman; Suzanne Satterfield; Hilsa Ayonayon; Clary Clish; Robert Gerszten; Tamara B Harris Journal: J Gerontol A Biol Sci Med Sci Date: 2019-01-01 Impact factor: 6.053
Authors: Dan Wang; Zaiming Luo; Xiaoyan Wang; Pedro A Jose; John R Falck; William J Welch; Shakil Aslam; Tom Teerlink; Christopher S Wilcox Journal: Hypertension Date: 2010-09-13 Impact factor: 10.190
Authors: Ellen R Brooks; Shannon Haymond; Alfred Rademaker; Christopher Pierce; Irene Helenowski; Rod Passman; Faye Vicente; Bradley A Warady; Susan L Furth; Craig B Langman Journal: Pediatr Nephrol Date: 2017-12-07 Impact factor: 3.714