Endothelium-Dependent Relaxation of Small Resistance... : Journal of the American Society of Nephrology (original) (raw)
Hemodynamics, Hypertension, and Vascular Regulation
Endothelium-Dependent Relaxation of Small Resistance Vessels Is Impaired in Patients with Autosomal Dominant Polycystic Kidney Disease
*Departments of Nephrology and Medicine, Herlev Hospital, Herlev, Denmark.
†Department of Clinical Physiology, Herlev Hospital, Herlev, Denmark.
Correspondence to Dr. Dan Wang, Department of Nephrology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Phone: +45 44883781; Fax: +45 44884615; E-mail: [email protected]
Accepted December 13, 1999
Received September 28, 1999
Abstract
Impaired endothelium-dependent relaxation has been demonstrated previously in resistance vessels of Han:SPRD polycystic kidney disease rats. The aim of the present study was to investigate whether endothelium-dependent relaxation is reduced also in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether this is influenced by the nitric oxide (NO) system. Small subcutaneous resistance vessels from normotensive ADPKD patients with normal or near-normal renal function (n = 9) and from healthy control subjects (n = 10) were mounted in a Mulvany-Halpern myograph. The morphology of the vessels and acetylcholine (ACh)-induced endothelium-dependent relaxation, as well as 3-morpholino-sydnonimine (SIN-1, NO donor)-induced endothelium-independent relaxation were investigated. The results showed that: (1) there were no significant differences in morphologic parameters of resistance vessels between the two groups; (2) the maximal ACh-induced relaxation rate was decreased in ADPKD patients compared with control subjects (71.5 ± 12.1 versus 85.2 ± 8.7%, P < 0.01); (3) in the presence of L-arginine (a substrate of NO synthase), a left shift of the ACh dose-response curves was found in control subjects, but not in ADPKD patients; (4) in the presence of the _N_G-nitro-L-arginine methyl ester (an inhibitor of NO synthase), a right shift of the ACh dose-response curve was found in control subjects, but not in ADPKD patients; and (5) endothelium-independent relaxation rate induced with SIN-1 was similar in patients and control subjects. In conclusion, endothelium-dependent relaxation was impaired in resistance vessels from patients with ADPKD. The reduced response of the vessels to both the substrate and inhibitor of NO synthase in ADPKD suggests that an impairment of NO synthase may be involved in the mechanism of endothelial dysfunction in ADPKD.
Copyright © 2000 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
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