Nephrol Dial Transplant (2000) 15: 1194-1200
© 2000 European Renal Association-European Dialysis and Transplant Association
Impaired endothelium-dependent vasodilatation in uraemia
1 The Renal Unit and 2 Department of Cardiology, Western Infirmary, Glasgow, UK
Background. Patients with chronic renal failure (CRF) have a substantially increased risk of cardiovascular death, the proposed mechanisms being arrhythmias (left ventricular hypertrophy) and accelerated atherosclerosis. The vascular endothelium protects against the development of atherosclerosis principally by releasing vasoactive substances such as nitric oxide (NO) and endothelium-derived hyperpolarizing factor. In CRF there is accumulation of endogenous inhibitors of NO synthesis. In this present study we assessed endothelium-dependent vasodilatation in patients with advanced uraemia.
Methods. Sixteen uraemic patients (pre-dialysis and continuous ambulatory peritoneal dialysis) and 18 controls were studied. Forearm plethysmography was used to measure forearm blood flow and the changes induced by carbachol (endothelium-dependent vasodilator) and sodium nitroprusside (SNP; endothelium-independent vasodilator). The order of drugs infused was randomized between subjects. Dose response curves were constructed for each agent and area under the curve (AUC) calculated (arbitrary units).
Results. Overall, vasodilatation to SNP and carbachol was similar between uraemic patients and controls. However, it became apparent that there was a marked order effect for the drugs infused, such that infusion of SNP as the first agent blunted the subsequent response to carbachol. When only those patients and controls who received carbachol followed by SNP were studied (10 in each group), the response to carbachol in uraemic patients was attenuated compared to controls: AUC (median(range)) for uraemic patients 529.0 (150.9–834.7) compared to AUC for controls 703.9 (583.5–1576.6); P=0.028. Vasodilatation to SNP was, however, similar between groups: AUC for uraemic patients 1475.0 (857.8–4717.1) compared to AUC for controls 1328.1 (216.6–3311.4); P=0.545.
Conclusions. This study has demonstrated a marked drug order effect not previously described for forearm plethysmography. When the order effect was taken into account, this study demonstrated reduced vasodilatation to carbachol in uraemic patients with a preserved response to SNP. This pattern indicates impaired endothelium-dependent vasodilatation in uraemic patients, a defect that may predispose this group to accelerated atherosclerosis.
Keywords: cardiovascular disease; forearm plethysmography; hypertension; nitric oxide; uraemia; vascular endothelium
Correspondence and offprint requests to: Dr Scott Morris, Renal Unit, Western Infirmary, Dumbarton Road, Glasgow G11 6NT, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Yigla, R. Banderski, Z. S. Azzam, S. A. Reisner, and F. Nakhoul Arterio-venous access in end-stage renal disease patients and pulmonary hypertension Therapeutic Advances in Respiratory Disease, April 1, 2008; 2(2): 49 - 53. [Abstract] [PDF]
|
|
|
|
 |
|
 J.-P. Stasch, P.M. Schmidt, P.I. Nedvetsky, T.Y. A. Nedvetskaya, H.S. Kumar, S. Meurer, M. Deile, A. Taye, A. Knorr, H. Lapp, et al. Endothelial Cell Dysfunction--Can One Outsmart Oxidative Stress by Direct Interaction with the Pathological Oxidized or Heme-Free Soluble Guanyl-Cyclase?: Targeting the Heme-Oxydized Nitric Oxide Receptor for Selective Vasodilatation of Diseased Blood Vessels. J Clin Invest 116: 2552-2561, 2006 J. Am. Soc. Nephrol., March 1, 2007; 18(3): 663 - 669. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Farkas, J. Nemcsik, E. Kolossvary, Z. Jarai, E. Nadory, C. Farsang, and I. Kiss Impairment of skin microvascular reactivity in hypertension and uraemia Nephrol. Dial. Transplant., September 1, 2005; 20(9): 1821 - 1827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mittermayer, G. Schaller, J. Pleiner, A. Vychytil, G. Sunder-Plassmann, W. H. Horl, and M. Wolzt Asymmetrical Dimethylarginine Plasma Concentrations Are Related to Basal Nitric Oxide Release but Not Endothelium-Dependent Vasodilation of Resistance Arteries in Peritoneal Dialysis Patients J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1832 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Goligorsky Endothelial cell dysfunction: can't live with it, how to live without it Am J Physiol Renal Physiol, May 1, 2005; 288(5): F871 - F880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stewart, A. Kohen, D. Brouder, F. Rahim, S. Adler, R. Garrick, and M. S. Goligorsky Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2687 - H2696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Amann, M.-L. Gross, and E. Ritz Pathophysiology Underlying Accelerated Atherogenesis in Renal Disease: Closing in on the Target J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1664 - 1666. [Full Text] [PDF]
|
|
|
|
|
|
M. Tepel Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia? Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1439 - 1442. [Full Text] [PDF]
|
|
|
|
|
|
M. Tepel Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia? Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1439 - 1442. [Full Text]
|
|
|
|
 |
|
 P. Koobi, J. Kalliovalkama, P. Jolma, J. Rysa, H. Ruskoaho, O. Vuolteenaho, M. Kahonen, I. Tikkanen, M. Fan, P. Ylitalo, et al. AT1 Receptor Blockade Improves Vasorelaxation in Experimental Renal Failure Hypertension, June 1, 2003; 41(6): 1364 - 1371. [Abstract] [Full Text] [PDF]
|
|