Back to Search
Start Over
Minoxidil improves vascular compliance, restores cerebral blood flow, and alters extracellular matrix gene expression in a model of chronic vascular stiffness
- Source :
- American journal of physiology. Heart and circulatory physiology. 315(1)
- Publication Year :
- 2018
-
Abstract
- Increased vascular stiffness correlates with a higher risk of cardiovascular complications in aging adults. Elastin (ELN) insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing. We used Eln+/− mice to test the hypothesis that pathologically increased vascular stiffness with concomitant arterial narrowing leads to decreased blood flow to end organs such as the brain. We also hypothesized that drugs that remodel arteries and increase lumen diameter would improve flow. To test these hypotheses, we compared carotid blood flow using ultrasound and cerebral blood flow using MRI-based arterial spin labeling in wild-type (WT) and Eln+/− mice. We then studied how minoxidil, an ATP-sensitive K+ channel opener and vasodilator, affects vessel mechanics, blood flow, and gene expression. Both carotid and cerebral blood flows were lower in Eln+/− mice than in WT mice. Treatment of Eln+/− mice with minoxidil lowered blood pressure and reduced functional arterial stiffness to WT levels. Minoxidil also improved arterial diameter and restored carotid and cerebral blood flows in Eln+/− mice. The beneficial effects persisted for weeks after drug removal. RNA-Seq analysis revealed differential expression of 127 extracellular matrix-related genes among the treatment groups. These results indicate that ELN insufficiency impairs end-organ perfusion, which may contribute to the increased cardiovascular risk. Minoxidil, despite lowering blood pressure, improves end-organ perfusion. Changes in matrix gene expression and persistence of treatment effects after drug withdrawal suggest arterial remodeling. Such remodeling may benefit patients with genetic or age-dependent ELN insufficiency. NEW & NOTEWORTHY Our work with a model of chronic vascular stiffness, the elastin ( Eln)+/− mouse, shows reduced brain perfusion as measured by carotid ultrasound and MRI arterial spin labeling. Vessel caliber, functional stiffness, and blood flow improved with minoxidil. The ATP-sensitive K+ channel opener increased Eln gene expression and altered 126 other matrix-associated genes.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Physiology
Vasodilator Agents
Perfusion scanning
Extracellular matrix
03 medical and health sciences
Mice
Vascular stiffness
Vascular Stiffness
Physiology (medical)
Internal medicine
Gene expression
medicine
Animals
biology
business.industry
Cerebral Arteries
medicine.disease
Elastin
Extracellular Matrix
Mice, Inbred C57BL
030104 developmental biology
Cerebral blood flow
Minoxidil
Cerebrovascular Circulation
Cardiology
Arterial stiffness
biology.protein
Cardiology and Cardiovascular Medicine
business
medicine.drug
Research Article
Subjects
Details
- ISSN :
- 15221539
- Volume :
- 315
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Accession number :
- edsair.doi.dedup.....e576d77a3d09b8e551075d798321d97f