title: Intravital imaging of the kidney in a rat model of salt-sensitive hypertension.
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 (GSCalb= 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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.|Department of Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Endres
authors.affiliation: Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.affiliation: Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: George J
authors.initials: GJ
authors.lastname: Rhodes
authors.affiliation: Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Silvia B
authors.initials: SB
authors.lastname: Campos-Bilderback
authors.affiliation: Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Kamocka
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Christopher
authors.initials: C
authors.lastname: McDermott-Roe
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors.forename: Alexander
authors.identifier: http://orcid.org/0000-0002-5190-8356
authors.initials: A
authors.lastname: Staruschenko
authors.affiliation: Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; ageurts@mcw.edu.|Department of Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors.forename: Aron M
authors.initials: AM
authors.lastname: Geurts
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D000069416:Intravital Microscopy; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D036641:Microscopy, Fluorescence, Multiphoton; D020303:Rats, Inbred Dahl; D065608:Renal Reabsorption; D012709:Serum Albumin / Q000378:metabolism; D017673:Sodium Chloride, Dietary; D013997:Time Factors
chemical_list: D012709:Serum Albumin; D017673:Sodium Chloride, Dietary
keywords: albuminuria; chronic kidney disease; glomerulus; proximal tubule