title: Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease.
abstract: Chronic kidney disease (CKD) and hypertension are co-morbid conditions both associated with altered resistance artery structure, biomechanics and function. We examined these characteristics in mesenteric artery together with renal function and systolic blood pressure (SBP) changes in the Lewis polycystic kidney (LPK) rat model of CKD. Animals were studied at early (6-weeks), intermediate (12-weeks), and late (18-weeks) time-points (n=21), relative to age-matched Lewis controls (n=29). At 12 and 18-weeks, LPK arteries exhibited eutrophic and hypertrophic inward remodelling characterised by thickened medial smooth muscle, decreased lumen diameter, and unchanged or increased media cross-sectional area, respectively. At these later time points, endothelium-dependent vasorelaxation was also compromised, associated with impaired endothelium-dependent hyperpolarisation and reduced nitric oxide synthase activity. Stiffness, elastic-modulus/stress slopes and collagen/elastin ratios were increased in 6 and 18-week-old-LPK, in contrast to greater arterial compliance at 12weeks. Multiple linear regression analysis highlighted SBP as the main predictor of wall-lumen ratio (r=0.536, P<0.001 n=46 pairs). Concentration-response curves revealed increased sensitivity to phenylephrine but not potassium chloride in 18-week-LPK. Our results indicate that impairment in LPK resistance vasculature is evident at 6weeks, and worsens with hypertension and progression of renal disease.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: jin_quek@hotmail.com.
authors.forename: K J
authors.initials: KJ
authors.lastname: Quek
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: rochelle.boyd@mq.edu.au.
authors.forename: R
authors.initials: R
authors.lastname: Boyd
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: omar_3m@yahoo.com.
authors.forename: O Z
authors.initials: OZ
authors.lastname: Ameer
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia; Centre for Eye Health, University of New South Wales, Sydney, Australia. Electronic address: bzangerl@cfeh.com.au.
authors.forename: B
authors.initials: B
authors.lastname: Zangerl
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: mark.butlin@mq.edu.au.
authors.forename: M
authors.initials: M
authors.lastname: Butlin
authors.affiliation: Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia. Electronic address: tim.murphy@unsw.edu.au.
authors.forename: T V
authors.initials: TV
authors.lastname: Murphy
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: alberto.avolio@mq.edu.au.
authors.forename: A P
authors.initials: AP
authors.lastname: Avolio
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: jacqueline.phillips@mq.edu.au.
authors.forename: J K
authors.initials: JK
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055119:Elastic Modulus; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D066253:Vascular Remodeling; D014655:Vascular Resistance / Q000187:drug effects; D059289:Vascular Stiffness; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents
keywords: Endothelium; Hypertension; Mesenteric resistance artery; Polycystic kidney disease; Vascular remodelling