Elastin insufficiency causes hypertension, structural defects and abnormal remodeling of renal vascular signaling

Elizabeth A. Owens; Li Jie; Beverly A.S. Reyes; Elisabeth J. Van Bockstaele; Patrick Osei-Owusu

doi:10.1016/j.kint.2017.04.044

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Elastin insufficiency causes hypertension, structural defects and abnormal remodeling of renal vascular signaling

Journal article

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Elastin insufficiency causes hypertension, structural defects and abnormal remodeling of renal vascular signaling

Elizabeth A. Owens, Li Jie, Beverly A.S. Reyes, Elisabeth J. Van Bockstaele and Patrick Osei-Owusu

Kidney international, v 92(5), pp 1100-1118

Nov 2017

DOI: https://doi.org/10.1016/j.kint.2017.04.044

PMID: 28754555

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Abstract

angiotensin receptors

elastin haploinsufficiency

extracellular matrix

hypertension

myogenic tone

renal function

Elastin deficiency causes vascular stiffening, a leading risk for hypertension and chronic kidney disease (CKD). The mechanisms mediating hypertension and/or CKD pathogenesis due to elastin deficiency are poorly understood. Using the elastin heterozygous (Eln+/−) mouse model, we tested whether renal dysfunction due to elastin deficiency occurs independently of and precedes the development of hypertension. We assessed blood pressure and renal hemodynamics in 30-day and 12-week-old male and female mice. At P30, blood pressure of Eln+/− mice was similar to wild-type controls; however, renal blood flow was lower, whereas renal vascular resistance was augmented at baseline in Eln+/− mice. At 12 weeks, renal vascular resistance remained elevated while filtration fraction was higher in male Eln+/− relative to wild-type mice. Heterozygous mice showed isolated systolic hypertension that was evident only at nighttime. Acute salt loading with 6% dietary sodium increased daytime systolic blood pressure only in male Eln+/− mice, causing a rightward shift and blunted slope of the pressure-natriuresis curve. Renal interlobar artery basal tone and myogenic response to increasing intraluminal pressure at day 10 were similar, whereas they were augmented at day 30 and at 12 weeks old in Eln+/− mice, and normalized by the AT1R blocker, candesartan. Heterozygous mice also exhibited podocyte foot process damage that persisted even when blood pressure was normalized to wild-type levels with hydralazine. Thus, elastin insufficiency triggers structural defects and abnormal remodeling of renal vascular signaling involving AT1R-mediated vascular mechanotransduction and renal hyperfiltration with increased blood pressure sensitivity to dietary sodium contributing to systolic hypertension.

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Details

Title: Elastin insufficiency causes hypertension, structural defects and abnormal remodeling of renal vascular signaling
Creators: Elizabeth A. Owens - Drexel University
Li Jie - Drexel University
Beverly A.S. Reyes - Drexel University
Elisabeth J. Van Bockstaele - Drexel University
Patrick Osei-Owusu - Drexel University
Publication Details: Kidney international, v 92(5), pp 1100-1118
Publisher: Elsevier
Resource Type: Journal article
Language: English
Academic Unit: Pharmacology and Physiology
Web of Science ID: WOS:000413267700014
Scopus ID: 2-s2.0-85025823020
Other Identifier: 991019167616504721

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Collaboration types: International collaboration
Web of Science research areas: Urology & Nephrology