Pathological alterations in resistance artery structure and biomechanics are commonly seen in association with hypertension. The present study used pressure myography and histology to investigate mesenteric resistance artery structural stiffness and morphology in a genetic hypertensive rat model of chronic kidney disease (CKD), the Lewis polycystic kidney (LPK) rat, at early (12 weeks; n=7) and established (18 weeks; n=7) CKD time-points, relative to agematched Lewis control rats (n=7 each). Animals were phenotyped for systolic blood pressure (SBP) and urine biochemistry. Animals were then euthanized (overdose isofluorane anaesthesia), blood collected for urea and creatinine analysis, and the mesenteric artery dissected. Twelve and 18 week-old LPK exhibited eutrophic and hypertrophic inward remodelling, characterized by increased medial smooth muscle thickness, decreased lumen diameter, and unchanged and increased media cross-sectional area (MCSA) in 12 and 18 week-old LPK, respectively, relative to age-matched Lewis controls. Structural changes were not associated with hyperplasia, as no age or strain-related changes in nuclear density or number were found. Larger elastic-modulus/stress slopes (EM/σ) and collagen/elastin ratios indicated increased stiffness in LPK at 18 weeks, relative to both age-matched Lewis and 12 week-old LPK (EM/σ: 24±2 vs. 6±0.3 and 5±1, respectively [P<0.001]; and collagen/elastin ratio: 8±2 vs. 2±0.5 and 4±1, respectively [P<0.05]). Regression analysis revealed SBP as a main predictor of wall/lumen ratio (R2=0.49, P=0.0003). These results indicate that mesenteric resistance arteries in the LPK model of CKD undergo vascular remodelling and stiffness. Hypertension likely predisposes to structural alterations in CKD.
|Number of pages||1|
|Journal||Journal of Vascular Research|
|Issue number||Supplement 2|
|Publication status||Published - 2014|
|Event||11th International Symposium on Resistance Arteries from Molecular Machinery to Clinical Challenges - Banff, Canada|
Duration: 7 Sep 2014 → 11 Sep 2014