Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease

被引:9
作者
Quek, K. J. [1 ]
Boyd, R. [1 ]
Ameer, O. Z. [1 ]
Zangerl, B. [1 ,2 ]
Butlin, M. [1 ]
Murphy, T. V. [3 ]
Avolio, A. P. [1 ]
Phillips, J. K. [1 ]
机构
[1] Macquarie Univ, Fac Med & Hlth Sci, Dept Biomed Sci, N Ryde, NSW 2109, Australia
[2] Univ New S Wales, Ctr Eye Hlth, Sydney, NSW, Australia
[3] Univ New S Wales, Sch Med Sci, Dept Physiol, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
Mesenteric resistance artery; Hypertension; Polycystic kidney disease; Endothelium; Vascular remodelling; SPONTANEOUSLY HYPERTENSIVE-RATS; SMOOTH-MUSCLE; DEPENDENT HYPERPOLARIZATION; CARDIOVASCULAR-DISEASE; MECHANICAL-PROPERTIES; NITRIC-OXIDE; CALCIFICATION; RESPONSIVENESS; HYPERTROPHY; RELAXATION;
D O I
10.1016/j.vph.2015.12.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 12 weeks. 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 6 weeks, and worsens with hypertension and progression of renal disease. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:42 / 52
页数:11
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