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

K. J. Quek, R. Boyd, O. Z. Ameer, B. Zangerl, M. Butlin, T. V. Murphy, A. P. Avolio, J. K. Phillips*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)42-52
Number of pages11
JournalVascular Pharmacology
Volume81
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Endothelium
  • Hypertension
  • Mesenteric resistance artery
  • Polycystic kidney disease
  • Vascular remodelling

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