Abstract: TH-PO550
Increased Basal Tone and Impaired Smooth Muscle Cell Contractility of the Carotid Artery in a CKD Rat Model
Session Information
- Bone and Mineral Metabolism: Basic
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Van den bergh, Geoffrey, University of Antwerp, Antwerp, antwerp, Belgium
- D'Haese, Patrick, University of Antwerp, Antwerp, antwerp, Belgium
- Verhulst, Anja, University of Antwerp, Antwerp, antwerp, Belgium
Background
Increased arterial stiffness (AS) is linked to aging and accelerated in patients with CKD. Traditionally, CKD has been closely associated with the development of arterial media calcifications (AMC), which together with changes in extracellular matrix composition are typical examples of passive stiffening. AS, on the other hand also has cellular, active components. Endothelial induced relaxation and vascular smooth muscle cell (VSMC) contractility, in response to pressure changes, are crucial to maintain a proper vessel tone. Using a CKD rat model this study aims to unravel the passive and active mechanisms underlying CKD related AS.
Methods
Eight Wistar rats were administered an adenine supplemented/phosphate rich diet for a period of 8 wks to induce CKD-related AMC, and compared to 8 age-matched control rats with normal renal function. Serum creatinine and phosphate were determined to follow up CKD development. AMC was investigated by measuring bulk Ca content in the aorta. AS was evaluated in vivo, using echo evaluation of the abdominal aorta pulse wave velocity (PWVa). An in house ex vivo organ bath setup to mimic cyclic stretch, was used to evaluate endothelial and VSMC functionality and to quantify the Peterson’s elastic modulus (Ep, measure of AS).
Results
As could be concluded from serum creatinine and phosphate levels, severe CKD developed in the adenine fed rats. Significantly higher Ca content in the aorta (p<0.01) of adenine rats confirmed AMC development. After 8 wks, adenine fed animals showed increased AS, both in vivo and ex vivo: significantly higher PWVa (p<0.01) and Ep (p<0.01) compared to controls. Furthermore, adenine rats have increased, pressure dependent, basal tone and diminished VSMC contractility (p<0.01).
Conclusion
The adenine rat model is suited to investigate the progressive character of AS. We observed an interplay between active and passive components. The reduction in VSMC contractility is detrimental for the arterial system to buffer pulsatile flows at higher pressures, further promoting AS. A logical next step would be to include earlier time points to study endothelial contribution and VSMC shift towards a pro-calcifying phenotype. Discovery of early mechanisms underlying AS will contribute to the development of novel AS preventive treatments.
Funding
- Government Support - Non-U.S.