+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Systemic Nitric Oxide Production Rate during Hemodialysis and Its Relationship with Nitric Oxide-Related Factors

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Background/Aims:Nitric oxide (NO) plays a key role in the regulation of vascular tone and controls both local and systemic hemodynamics. Here, we estimated systemic NO production rates of hemodialysis (HD) patients, based on the time course of plasma concentration of nitrate (an oxidative end product of NO) and investigated possible roles of NO-related factors. Methods: We measured plasma concentrations of nitrate, L-arginine (a substrate of NO synthase: NOS), asymmetric dimethylarginine (ADMA, an endogenous NOS inhibitor), tetrahydrobiopterin (BH<sub>4</sub>, a NOS cofactor), dihydrobiopterin (BH<sub>2</sub>, an oxidized form of BH<sub>4</sub>) and oxidized low-density lipoprotein (oxyLDL; an index of oxidative stress) before and after 30-min and 4-hour HD (n = 10). Results:The time-averaged NO production rate during HD was estimated by fitting the time course of plasma nitrate concentration with a single-compartment model (4.00 ± 0.82 µmol/min, 4.99 ± 1.08 µmol/kg/h). The L-arginine/ADMA ratio ( L-arginine availability) after 30-min HD showed a positive correlation with the NO production rate (p < 0.05). Conclusion: The systemic NO production rate during HD could be estimated by the single-compartment analysis. The L-arginine/ADMA ratio seems to play an important role in the regulation of the NO production during HD.

          Related collections

          Most cited references 19

          • Record: found
          • Abstract: found
          • Article: not found

          Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase.

          Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure, hypertension, and chronic heart failure. In patients with renal failure, plasma ADMA levels are an independent correlate of left ventricular ejection fraction. However, the cardiovascular effects of a systemic increase in ADMA in humans are not known. In a randomized, double-blind, placebo-controlled study in 12 healthy male volunteers, we compared the effects of intravenous low-dose ADMA and placebo on heart rate, blood pressure, cardiac output, and systemic vascular resistance at rest and during exercise. We also tested the hypothesis that ADMA is metabolized in humans in vivo by dimethylarginine dimethylaminohydrolase (DDAH) enzymes. Low-dose ADMA reduced heart rate by 9.2+/-1.4% from 58.9+/-2.0 bpm (P<0.001) and cardiac output by 14.8+/-1.2% from 4.4+/-0.3 L/min (P<0.001). ADMA also increased mean blood pressure by 6.0+/-1.2% from 88.6+/-3.4 mm Hg (P<0.005) and SVR by 23.7+/-2.1% from 1639.0+/-91.6 dyne. s. cm-5 (P<0.001). Handgrip exercise increased cardiac output in control subjects by 96.8+/-23.3%, but in subjects given ADMA, cardiac output increased by only 35.3+/-10.6% (P<0.05). DDAHs metabolize ADMA to citrulline and dimethylamine. Urinary dimethylamine to creatinine ratios significantly increased from 1.26+/-0.32 to 2.73+/-0.59 after ADMA injection (P<0.01). We estimate that humans generate approximately 300 micromol of ADMA per day, of which approximately 250 micromol is metabolized by DDAHs. This study defines the cardiovascular effects of a systemic increase in ADMA in humans. These are similar to changes seen in diseases associated with ADMA accumulation. Finally, our data also indicate that ADMA is metabolized by DDAHs extensively in humans in vivo.
            • Record: found
            • Abstract: found
            • Article: not found

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

            A deficiency of the endogenous vasodilator nitric oxide (NO) has been implicated as a potential cause of hypertension in chronic renal disease (CRD) patients. This study was conducted to determine whether 24-hour NOX (NO2 and NO3) excretion (a qualitative index of total NO production) is reduced in patients with CRD. Measurements were made in 13 CRD patients and 9 normotensive healthy controls after 48 hours on a controlled low-NOX diet. Urine was collected 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 synthesis), and the endogenous NO synthesis inhibitor asymmetrical dimethylarginine (ADMA) and its inert isomer and symmetrical dimethylarginine (SDMA) were also determined. Systolic blood pressure was higher in CRD patients (12 of whom were already on antihypertensive therapy) than in controls (P < 0.05). Twenty-four-hour urinary NOX excretion was low in CRD patients compared with controls despite similar dietary NO intake, suggesting that net endogenous NO production is decreased in renal disease. In contrast, the 24-hour urinary cGMP did not correlate with UNOXV. Plasma citrulline was increased in CRD patients, possibly reflecting reduced conversion of citrulline to arginine. Plasma arginine was not different, and plasma ADMA levels were elevated in CRD versus controls, changes that would tend to lower NO synthase. These results suggest that NO production is low in CRD patients and may contribute to hypertension and disease progression in CRD.
              • Record: found
              • Abstract: found
              • Article: not found

              Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin.

              Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                September 2005
                04 October 2005
                : 23
                : 4
                : 317-324
                aDepartment of Medical Engineering, Kawasaki Medical School, Kurashiki, bRenal Center, Kawasaki Medical School Hospital, Kurashiki, cDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine and Dentistry, Okayama, dDepartment of Nutritional Science, Okayama Prefectural University, Soja, and eDepartment of Nephrology, Kawasaki Medical School, Kurashiki, Japan
                87769 Blood Purif 2005;23:317–324
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 37, Pages: 8
                Self URI (application/pdf):
                Original Paper


                Comment on this article