Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

We developed an online continuous hemodiafiltration (CHDF) system with a central reverse osmosis (RO) fluid delivery system in 1996. This was improved to a system composed of a single-patient dialysis machine and RO module in 2003. This comprises a water treatment system, an RO module, a dialysis machine with 3 endotoxin retentive filters, 2 additional roller pump units, and a disposable special circuit. Dialysate is produced online by a dialysis machine using RO water and dialysate concentrate, which passes through endotoxin retentive filters and is supplied via the machine in the usual manner. A disposable special circuit and additional two roller pumps independently regulate dialysate flow and substitute flow from 0 to 12 in steps of 0.1 l/h. Seventy-seven patients with acute kidney injury (AKI) were treated with online CHDF from December 1996 to June 2004. Patient outcome was compared with the other modality of continuous renal replacement therapy from July 1992 to June 2004. The survival rates of each modality were 68.3, 65.0, 56.6 and 74.0% for conventional CHDF, high-flow continuous hemodialysis, high-flow CHDF and high-flow/high-volume CHDF (online CHDF), respectively. The survival rate of the high-volume modality (online CHDF) group was significantly higher (p = 0.046) than that of the low volume modality group (61.1%). Increases in efficacy and efficiency are a challenge facing blood purification therapy, and, moreover, individualized prescriptions are crucial in AKI patients in ICU. However, the cost of the dialysate and substitution fluid is a limitation of the therapy. The greatest advantage of the system is that a very high dose of delivered dialysate and substitute does not lead to a proportional rise in the cost. The online CHDF system is currently one of the most feasible solutions.

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