Endogenous nitric oxide synthase inhibitors and renal perfusion in patients with heart failure

Background Patients with heart failure are characterized by impaired nitric oxide-dependent endothelial vasodilation and, in addition, by reduced renal perfusion. Design We assessed blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal haemodynamics to compare normotensive patients with mild heart failure (n = 12, seven males, 70 +/- 1 years, 72.0 +/- 2.7 kg, 92 +/- 2 mmHg, NYHA I/II) and healthy subjects matched with respect to gender, age and body weight (n = 12, seven males, 69 +/- 2 years, 72.7 +/- 2.5 kg, 88 +/- 2 mmHg). Results Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P < 0.01) and effective renal plasma flow (ERPF) significantly lower (P < 0.01) in the patients with heart failure (ADMA 4.18 +/- 0.42 mumol L-1 , RVR 159 +/- 12 mmHg mL(-1) min(-1) , ERPF 381 +/- 26 mL min(-1) 1.73 m(-2) ) as compared with the healthy controls (ADMA 2.38 +/- 0.11 mumol L-1 , RVR 117 +/- 8 mmHg mL(-1) min(-1) , ERPF 496 +/- 19 mL min(-1) 1.73 m(-2) ). In contrast, plasma concentrations of l-arginine, homocysteine, symmetric dimethylarginine (i.e. the biologically inactive stereoisomer of ADMA) and plasma renin activity were not significantly different in both groups studied. In the multiple regression analysis, only plasma ADMA concentrations independently predicted reduced ERPF (r = -0.57; P < 0.003). Conclusions In normotensive patients with heart failure plasma ADMA concentrations are markedly increased and related to reduced renal perfusion. Thus accumulation of this endogenous nitric oxide inhibitor may play a role in renal pathology in these patients.