Clear Correlation of Tetrahydrobiopterin with Nitric Oxide Bioavailability in Continuous Ambulatory Peritoneal Dialysis

have been no investigations on the roles of NO and BH 4 in CAPD. Therefore, we measured both NO and BH 4 concentrations in spent dialysates of CAPD patients to investigate the relation between the two. The NO concentration was measured by an NO sensor [6, 12] and BH 4 and BH 2 concentrations were measured fluorometrically by the HPLC-based method [13] . This study protocol was approved by the Ethical Committee of Kawasaki Medical School. Written informed consent was obtained from each patient. Nitric oxide (NO) plays diverse physiological roles including vasodilatory and anti-atherogenic actions [1] . In continuous ambulatory peritoneal dialysis (CAPD), NO has been thought to regulate permeability of the peritoneal membrane and suppress angiogenesis in the peritoneum [2–4] . Thus, abnormal production and/or metabolism of NO would lead to peritoneal dysfunctions. Previous studies suggested that changes in NO bioavailability induce the dysfunction of peritoneal membranes [3, 5] . Recently, we demonstrated that NO exists in spent dialysates at measurable levels over a wide range [6] . Tetrahydrobiopterin (BH 4 ) is a cofactor for NO synthase (NOS) and plays an important role in maintaining the NOS activity. Depletion of BH 4 would result in NOS uncoupling and NOS-derived superoxide release [1, 7, 8] . Yokoyama et al. [9] reported that a significant positive correlation between creatinine clearance and the BH 4 /BH 2 ratio (BH 2 = biopterin, an oxidized form of BH 4 ) in the patients with chronic renal failure. Yamamizu et al. [10] demonstrated the involvement of BH 4 deficiency in endothelial dysfunction in rats with chronic renal failure. Recently, we also reported the possible involvement of BH 4 in the NO production rate of hemodialysis (HD) patients [11] . However, there Published online: July 13, 2010