Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

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Abstract

Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin- converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10±1 × 10 3 to 17±2 × 10 3 μm 2; 6 weeks: 13±2 × 10 3 to 24±3 × 10 3 μm 2). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (O: 385±13 to 463±14 μm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 × 10 3 ±1 × 10 3 μm 2). The diameter of the HF arteries of normotensive rats increased (O: 463±22 μm) but no expansion occurred in the HF arteries of hypertensive rats (O: 471±16 μm). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (O: 419±13 to 475±16 μm). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean O between 235 and 290 μm), and infiltration of monocyte/macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition. © 2012 The Japanese Society of Hypertension All rights reserved.

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Lemkens, P., Nelissen, J., Meens, M. J. P. M. T., Fazzi, G. E., Janssen, G. J. M., Debets, J. J. M., … De Mey, J. G. R. (2012). Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats. Hypertension Research, 35(11), 1093–1101. https://doi.org/10.1038/hr.2012.94

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