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Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H1008-16. doi: 10.1152/ajpheart.00288.2015. Epub 2015 Jul 31.

Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness.

Author information

1
Departments of Pediatrics Washington University School of Medicine, St. Louis, Missouri; and.
2
Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.
3
Departments of Pediatrics Washington University School of Medicine, St. Louis, Missouri; and kozel_b@kids.wustl.edu.

Abstract

Increased arterial stiffness is a common characteristic of humans with Williams-Beuren syndrome and mouse models of elastin insufficiency. Arterial stiffness is associated with multiple negative cardiovascular outcomes, including myocardial infarction, stroke, and sudden death. Therefore, identifying therapeutic interventions that improve arterial stiffness in response to changes in elastin levels is of vital importance. The goal of this study was to determine the effect of chronic pharmacologic therapy with different classes of antihypertensive medications on arterial stiffness in elastin insufficiency. Elastin-insufficient mice 4-6 wk of age and wild-type littermates were subcutaneously implanted with osmotic micropumps delivering a continuous dose of one of the following: vehicle, losartan, nicardipine, or propranolol for 8 wk. At the end of treatment period, arterial blood pressure and large artery compliance and remodeling were assessed. Our results show that losartan and nicardipine treatment lowered blood pressure and pulse pressure in elastin-insufficient mice. Elastin and collagen content of abdominal aortas as well as ascending aorta and carotid artery biomechanics were not affected by any of the drug treatments in either genotype. By reducing pulse pressure and shifting the working pressure range of an artery to a more compliant region of the pressure-diameter curve, antihypertensive medications may mitigate the consequences of arterial stiffness, an effect that is drug class independent. These data emphasize the importance of early recognition and long-term management of hypertension in Williams-Beuren syndrome and elastin insufficiency.

KEYWORDS:

Williams-Beuren syndrome; arterial stiffness; elastin; hypertension; pulse pressure

PMID:
26232234
PMCID:
PMC4591401
DOI:
10.1152/ajpheart.00288.2015
[Indexed for MEDLINE]
Free PMC Article

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