title: Endothelium-dependent relaxation of small resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease.
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.
authors.affiliation: Departments of Nephrology and Medicine, Herlev Hospital, Herlev, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Clinical Physiology, Herlev Hospital, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Iversen
authors.affiliation: Departments of Nephrology and Medicine, Herlev Hospital, Herlev, Denmark.
authors.forename: Svend
authors.initials: S
authors.lastname: Strandgaard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016891:Polycystic Kidney, Autosomal Dominant / Q000473:pathology / Q000503:physiopathology*; D012016:Reference Values; D012867:Skin / Q000098:blood supply; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester