Abstract
BackgroundHypertension is a well-established driver of vascular remodeling and stiffening. The goal of this study was to evaluate whether restoring normal blood pressure (BP) fully restores vascular stiffness toward that of normotensive controls.MethodsC57Bl6/J male mice received angiotensin II (angII; 1 μg/kg/min) via infusion pump for 8 weeks (hypertension group: HH), angII for 4 weeks (hypertension group: H4), angII for 4 weeks followed by 4 weeks of recovery (reversal group: HN), or sham treatment (normotensive group: NN). BP, heart rate, and pulse wave velocity (PWV) were measured longitudinally. At the end of the study period, aortas were harvested for testing of vasoreactivity, passive mechanical properties, and vessel structure.ResultsThe HH group exhibited a sustained increase in BP and PWV over the 8-week period (p < 0.01). In the HN group, BP and PWV increased during the 4-week angII infusion, and, though BP was restored during the 4-week recovery, PWV exhibited only partial restoration (p < 0.05). Heart rate was similar in all cohorts. Compared to NN controls, both HH and HN groups had significantly increased wall thickness (p < 0.05 HH vs. NN, p < 0.01 HN vs. NN), mucosal extracellular matrix accumulation (p < 0.0001 HH vs. NN, p < 0.05 HN vs. NN), and intralamellar distance (p < 0.001 HH vs. NN, p < 0.01 HN vs. NN). Both intact and decellularized vessels were noted to have significantly higher passive stiffness in the HH and H4 cohorts than in NN controls (p < 0.0001). However, in the HN cohort, intact vessels were only modestly stiffer than those of NN controls, and decellularized HN vessels were identical to those from the NN controls. Compared to NN controls, the HH and HN cohorts exhibited significantly diminished phenylephrine-induced contraction (p < 0.0001) and endothelium-dependent vasodilation (p < 0.05).ConclusionHypertension causes a significant increase in in vivo aortic stiffness that is only partially reversible after BP normalization. Although hypertension does lead to matrix stiffening, restoration of BP restores matrix mechanics to levels similar to those of normotensive controls. Nevertheless, endothelial and vascular smooth muscle cell dysfunction persist after restoration of normotension. This dysfunction is, in part, responsible for augmented PWV after restoration of BP.
Highlights
Hypertension is a multifactorial disease that is associated with a multitude of comorbidities, such as vascular stiffness (Franklin and Levy, 2011; Steppan et al, 2011; AlGhatrif et al, 2013; Verwoert et al, 2014)
Given the significant contribution of vascular SMCs (VSMCs) to the overall vascular modulus identified by pulse wave velocity (PWV) measurement and tensile testing, we evaluated the vasoreactivity of the descending thoracic aorta at the end of the study period (8 weeks)
Monassier and El Fertak, 2006), we showed that the induction of hypertension leads to vascular remodeling and overall stiffening of the aorta as a result of both passive vascular matrix stiffening and contributions from VSMCs
Summary
Hypertension is a multifactorial disease that is associated with a multitude of comorbidities, such as vascular stiffness (Franklin and Levy, 2011; Steppan et al, 2011; AlGhatrif et al, 2013; Verwoert et al, 2014). Mechanical forces that regulate endothelial cells include hoop stress imposed by the mean arterial pressure (MAP) and shear stress due to blood flow (Humphrey et al, 2015) The latter in particular is a key regulator of endothelial nitric oxide synthase-dependent nitric oxide production and endothelial function and thence, vascular tone and smooth muscle cell (SMC) function (Davis et al, 2001; Boo et al, 2002a,b; Verwoert et al, 2014). The vascular matrix and the vascular SMCs (VSMCs) are the main load-bearing elements in the vessel wall, and subtle changes in either can result in a remarkable increase in overall vascular stiffness. This stiffening of the vasculature leads to higher systolic and lower diastolic BP, which increases shear stress and can hasten the development of atherosclerosis. The goal of this study was to evaluate whether restoring normal blood pressure (BP) fully restores vascular stiffness toward that of normotensive controls
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
