Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects

Background-Reduced availability of nitric oxide (NO) is thought to contribute to the age-associated increase of renovascular tone and blood pressure. We assessed blood concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal hemodynamics, comparing young (n=24, 13 men, 25+/-1 years) and elderly (n=24, 13 men, 69+/-2 years) healthy subjects and elderly subjects with essential hypertension (n=24, 13 men, 70+/-2 years). Methods and Results-Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P<0.05) and effective renal plasma flow (ERPF) significantly lower (P<0.05) in elderly (2.77+/-0.20 mumol/L, 125+/-10 mm Hg/mL per minute, 487+/-26 mL/min per 1.73 m(2)) than in young healthy subjects (1.30+/-0.11, 77+/-3, 654+/-18). Both ADMA levels and RVR were higher and ERPF lower in the hypertensive elderly subjects (3.53+/-0.23, 163+/-11, 427+/-19; P<0.05 versus both groups). In contrast, plasma concentrations of the biologically inactive stereoisomer symmetric dimethylarginine, L-arginine, and homocysteine were similar in the 3 groups studied. In the logistic regression analysis only ADMA was an independent determinant of both ERPF (P<0.001; r(2)=0.80) and RVR (P<0.002; r(2)=0.86). In addition, ADMA (P<0.002) and serum glucose (P<0.036) were independently related (r(2)=0.67) to the level of blood pressure. Conclusions-These results are compatible with the notion that accumulation of the endogenous NO synthase inhibitor ADMA in senescent individuals is involved in the decrease of renal perfusion and increase of blood pressure.