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Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats.
- Source :
-
Hypertension research : official journal of the Japanese Society of Hypertension [Hypertens Res] 2012 Nov; Vol. 35 (11), pp. 1093-101. Date of Electronic Publication: 2012 Jul 12. - Publication Year :
- 2012
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1348-4214
- Volume :
- 35
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Hypertension research : official journal of the Japanese Society of Hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 22786567
- Full Text :
- https://doi.org/10.1038/hr.2012.94