1. Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats.
- Author
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Lemkens P, Nelissen J, Meens MJ, Fazzi GE, Janssen GJ, Debets JJ, Janssen BJ, Schiffers PM, and De Mey JG
- Subjects
- Animals, Aspartic Acid Endopeptidases antagonists & inhibitors, Aspartic Acid Endopeptidases drug effects, Benzazepines pharmacology, Blood Pressure drug effects, Cell Movement drug effects, Cell Movement physiology, Disease Models, Animal, Endothelin-Converting Enzymes, Enzyme Inhibitors pharmacology, Hypertension chemically induced, Hypertrophy chemically induced, Macrophages pathology, Metalloendopeptidases antagonists & inhibitors, Metalloendopeptidases drug effects, Monocytes pathology, Neprilysin antagonists & inhibitors, Neprilysin drug effects, Rats, Rats, Wistar, Regional Blood Flow drug effects, Vascular Resistance drug effects, Vascular Resistance physiology, Blood Pressure physiology, Desoxycorticosterone adverse effects, Hypertension pathology, Hypertension physiopathology, Mesenteric Arteries pathology, Mesenteric Arteries physiopathology, Regional Blood Flow physiology
- 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 (Ø: 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 (Ø: 463±22 μm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471±16 μm). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (Ø: 419±13 to 475±16 μm). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean Ø 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.
- Published
- 2012
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