Abstract
Hypertension Mechanisms: Elastin Haploinsufficiency Alters Renal Structure and Function
The FASEB journal, v 30(S1)
Apr 2016
Abstract
Abstract only
Hypertension is a hallmark of Williams syndrome, an autosomal‐dominant disease caused partly by loss‐of‐function mutations or gene deletions resulting in elastin (
Eln
) haploinsufficiency. Hypertension is a leading risk for several cardiovascular diseases including heart failure, stroke, chronic kidney disease, and renal failure. The mechanisms underlying hypertension due to elastin insufficiency are poorly understood. Because the kidney plays a critical role in long‐term blood pressure (BP) control, we determined whether
Eln
haploinsufficiency affects renal structure and function to contribute to hypertension development. We determined the effects of hypertension on wild type (WT) and
Eln+
/− mouse kidney structure using histology and electron microscopy. Kidney function was assessed by measuring renal blood flow, glomerular filtration rate (GFR), urine output, sodium and potassium excretion, and proteinuria. We found that
Eln+
/− mice had glomerular podocyte effacement accompanied by increased BP, renal vascular resistance (RVR), urine output and sodium excretion rate. However, GFR was only slightly elevated in
Eln+
/− mice. Systemic angiotensin type 1 receptor blockade with candesartan decreased RVR and BP in female
Eln+
/− mice to levels in WT controls.
Ex vivo
pressurized vessel studies showed increased myogenic tone accompanied by increased wall tension and wall strain in interlobar arteries from
Eln+/
− mice. We conclude that
Eln
haploinsufficiency causes renal vascular dysfunction, which contributes to the development of hypertension. Such a prolonged systemic BP elevation leads to glomerular structural damage due to high renal perfusion pressure. Therefore, therapies that control BP in patients with elastin deficiency may be beneficial in preventing hypertension‐evoked kidney damage.
Support or Funding Information
Margaret Q. Landenberger Research Foundation Grant
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Details
- Title
- Hypertension Mechanisms: Elastin Haploinsufficiency Alters Renal Structure and Function
- Creators
- Patrick Osei-Owusu - Drexel UniversityElizabeth A Owens - Drexel UniversityLi Jie - Pharmacology and Physiology Drexel University Philadelphia PABeverly A Reyes - Drexel UniversityElisabeth J Van Bockstaele - Drexel University
- Publication Details
- The FASEB journal, v 30(S1)
- Publisher
- Wiley
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Other Identifier
- 991021903119704721