title: Differential microvasculature dysfunction in living kidney donor transplant recipients: nondialyzed versus dialyzed chronic kidney disease patients.
abstract: We hypothesized that there was differential vasomotor dysfunction in the microcirculation between nondialyzed and dialyzed chronic kidney disease (CKD) patients. During live donor kidney transplantation procedures, skin arterioles (SkA; internal diameter = 120 +/- 5 microm) from donors (n = 27) and recipients (nondialysis = 15; dialysis = 20) were dissected from the abdominal wall at the incision site. In vivo aortic pulse wave velocity (PWV) was also measured. In the in vitro isometric force measurement, nondialyzed SkA exhibited comparable contraction to donor SkA, whereas dialyzed SkA had 60 and 40-50% increase in contraction in response to depolarization and agonist (that is, phenylephrine, serotonin and endothelin-1) stimulation, respectively. The acetylcholine-induced relaxation in the nondialyzed SkA was decreased by 50% compared with dialyzed SkA. However, pre-incubation with superoxide dismutase greatly enhanced the relaxation response in the nondialyzed, but not in the dialyzed SkA and donor SkA. Pre-incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) elevated the resting tension and left-shifted the concentration response curve of phenylephrine-stimulated contraction in the donor-SkA. L-NAME only increased the resting tension in the nondialyzed vessel. In vitro stiffness positively correlated with PWV (R(2) = 0.302, p = 0.001), and dialyzed SkA was 60% stiffer than nondialyzed and donor SkA. The acetylcholine relaxation was negatively correlated with PWV in donors and recipients (R(2) = 0.282, p = 0.01). In conclusion, we have uniquely demonstrated differential microvasculature dysfunction between nondialyzed and dialyzed CKD patients.
authors.affiliation: Department of Cardiovascular Science, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. adawingyee@yahoo.ca
authors.forename: Ada W Y
authors.initials: AW
authors.lastname: Chung
authors.forename: H H Clarice
authors.initials: HH
authors.lastname: Yang
authors.forename: Mhairi K
authors.initials: MK
authors.lastname: Sigrist
authors.forename: Elliott
authors.initials: E
authors.lastname: Chum
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Booth
authors.forename: William A
authors.initials: WA
authors.lastname: Gourlay
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
mesh_terms: D001160:Arterioles / Q000503:physiopathology; D002908:Chronic Disease; D003187:Compliance; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006435:Renal Dialysis; D012867:Skin / Q000098:blood supply*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase