Minoxidil improves vascular compliance, restores cerebral blood flow, and alters extracellular matrix gene expression in a model of chronic vascular stiffness

American Journal of Physiology. Heart and Circulatory Physiology
Russell H KnutsenBeth A Kozel

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 persist...Continue Reading

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Citations

Sep 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Maria BloksgaardLuis A Martinez-Lemus
Apr 11, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Austin J CoccioloneJessica E Wagenseil
Jul 5, 2019·Biomechanics and Modeling in Mechanobiology·Jungsil KimJessica E Wagenseil
Nov 10, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Nick R WinderAshley E Walker
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Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin ZimmermanJacob Raber
Aug 21, 2021·Exploration of Medicine·Lova Prasadareddy KajuluriKathleen G Morgan

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Datasets Mentioned

BETA
GSE110296

Methods Mentioned

BETA
pharmacotherapy
genotyping
ELISA
Hi-Seq
RNA-Seq
profiler

Software Mentioned

featureCounts
STAR
: profiler
JMP
Chart
R
DESeq2
profiler
NDP
ImageJ

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