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

Carmen M. Halabi, Thomas J. Broekelmann, Russell H. Knutsen, Li Ye, Robert P. Mecham, Beth A. Kozel

Research output: Contribution to journalArticle

11 Scopus citations

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 pressurediameter 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 longterm management of hypertension in Williams-Beuren syndrome and elastin insufficiency.

Original languageEnglish
Pages (from-to)H1008-H1016
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number5
DOIs
StatePublished - Sep 3 2015

Keywords

  • Arterial stiffness
  • Elastin
  • Hypertension
  • Pulse pressure
  • Williams- Beuren syndrome

Fingerprint Dive into the research topics of 'Chronic antihypertensive treatment improves pulse pressure but not large artery mechanics in a mouse model of congenital vascular stiffness'. Together they form a unique fingerprint.

  • Cite this