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Intravital imaging of the kidney in a rat model of salt-sensitive hypertension. Am J Physiol Renal Physiol 2017 Aug 01;313(2):F163-F173

Date

04/14/2017

Pubmed ID

28404591

Pubmed Central ID

PMC5582897

DOI

10.1152/ajprenal.00466.2016

Scopus ID

2-s2.0-85026777997   5 Citations

Abstract

Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension. Following a high-salt diet, SS rats exhibited elevated blood pressure, increased glomerular sieving of albumin (GSC = 0.0686), relative permeability to albumin (+Δ16%), and impaired volume hemodynamics (-Δ14%). Serum albumin but not serum globulins or creatinine concentration was decreased (-0.54 g/dl), which was concomitant with increased filtration of albumin (3.7 vs. 0.8 g/day normal diet). Pathologically, hypertensive animals had significant tubular damage, as indicated by increased prevalence of granular casts, expansion and necrosis of PT epithelial cells (+Δ2.20 score/image), progressive augmentation of red blood cell velocity (+Δ269 µm/s) and micro vessel diameter (+Δ4.3 µm), and increased vascular injury (+Δ0.61 leakage/image). Therefore, development of salt-induced hypertension can be triggered by fast and progressive pathogenic remodeling of PT epithelia, which can be associated with changes in albumin handling. Collectively, these results indicate that both the glomerulus and the PT contribute to albuminuria, and dual treatment of glomerular filtration and albumin reabsorption may represent an effective treatment of salt-sensitive hypertension.

Author List

Endres BT, Sandoval RM, Rhodes GJ, Campos-Bilderback SB, Kamocka MM, McDermott-Roe C, Staruschenko A, Molitoris BA, Geurts AM, Palygin O

Authors

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Oleg Palygin PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Alexander V. Staruschenko PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Albuminuria
Animals
Blood Pressure
Disease Models, Animal
Glomerular Filtration Rate
Hypertension
Intravital Microscopy
Kidney Glomerulus
Kidney Tubules, Proximal
Microscopy, Fluorescence, Multiphoton
Rats, Inbred Dahl
Renal Reabsorption
Serum Albumin
Sodium Chloride, Dietary
Time Factors
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75