Total nitric oxide production is low in patients with chronic renal disease

Background A deficiency of the endogenous vasodilator nitric oxide (NO) has been implicated as a potential cause of hypertension in chronic renal dise ase (CRD) patients. This study was conducted to determine whether 24-hour N Ox (NO2 and NO3) excretion (a qualitative index of total NO production) is reduced in patients with CRD. Methods. Measurements were made in 13 CRD patients and 9 normotensive healt hy controls after 48 hours on a controlled low-NOx diet. Urine was collecte d over the second 24-hour period for analysis of 24-hour NOx, and cGMP and blood drawn at the completion. Plasma levels of arginine (the substrate for endogenous renal NO synthesis), citrulline (substrate for renal arginine s ynthesis), and the endogenous NO synthesis inhibitor asymmetrical dimethyla rginine (ADMA) and its inert isomer and symmetrical dimethylarginine (SDMA) were also determined. Results. Systolic blood pressure was higher in CRD patients (12 of whom wer e already on antihypertensive therapy) than in controls (P < 0.05). Twenty- four-hour urinary NOx excretion was low in CRD patients compared with contr ols despite similar dietary NO intake, suggesting that net endogenous NO pr oduction is decreased in renal disease. In contrast, the 24-hour urinary cG MP did not correlate with UNOXV. Plasma citrulline was increased in CRD pat ients, possibly reflecting reduced conversion of citrulline to arginine. Pl asma arginine was not different, and plasma ADMA levels were elevated in CR D versus controls, changes that would tend to lower NO synthase. Conclusion. These results suggest that NO production is low in CRD patients and may contribute to hypertension and disease progression in CRD.