Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis – a randomized cross-over study

BMC Nephrology

Research Article

Mias Pretorius¹  Nancy J. Brown²  Katie C. Sprinkel²  Jorge L. Gamboa²  T. Alp Ikizler³ 

[1] Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA;Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2222 Pierce Avenue, 561-B PRB, 37232, Nashville, TN, USA;Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA;

关键词: Asymmetric dimethylarginine;    Hemodialysis;    Angiotensin converting enzyme inhibitors;    Angiotensin receptor blocker;   

DOI  :  10.1186/s12882-015-0162-x

 received in 2015-03-10, accepted in 2015-10-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundEndothelial dysfunction occurs in patients with end-stage renal disease (ESRD) and is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) contributes to endothelial dysfunction in ESRD. In the general population, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease ADMA levels, but no study has compared the effect of these drugs in patients with ESRD on maintenance hemodialysis (MHD).MethodsWe evaluated the effect of 1-week treatment with ramipril (5 mg/d), valsartan (160 mg/d), and placebo on ADMA levels in 15 patients on MHD in a double-blind, placebo-controlled, three x three cross-over study.ResultsWe found that ADMA levels were increased at baseline and throughout the dialysis session during ramipril treatment (p < 0.001 compared to both, placebo and valsartan). Ramipril did not increase ADMA levels in a study of patients without ESRD, suggesting that factors related to ESRD or hemodialysis contribute to the ACE inhibitor-induced increase in ADMA. We have previously shown that ACE inhibition increases bradykinin (BK) levels during hemodialysis. We therefore evaluated the effect of bradykinin on ADMA production in A549 cells; a cell line that expresses BK receptors. Incubation with BK increased intracellular ADMA concentration through BK B2-receptor stimulation.ConclusionThese data indicate that short-term ACE inhibition increases ADMA in patients on MHD whereas ARBs do not. In vitro studies further suggest that this may occur through BK-mediated increase in ADMA production during ACE inhibition.Trial registrationClinicaltrials.gov NCT00732069 August 6 2008 and NCT00607672 February 4 2008

【 授权许可】

CC BY   
© Gamboa et al. 2015