Intravital imaging of the kidney in a rat model of salt-sensitive hypertension

Bradley T. Endres, Ruben M. Sandoval, George J. Rhodes, Silvia Campos-Bilderback, Malgorzata Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce Molitoris, Aron M. Geurts, Oleg Palygin

Research output: Contribution to journalArticle

6 Scopus 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-photonbased 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 (+∆16%), and impaired volume hemodynamics (-∆14%). 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 (+∆2.20 score/image), progressive augmentation of red blood cell velocity (+∆269 μm/s) and micro vessel diameter (+∆4.3 μm), and increased vascular injury (+∆0.61 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.

Original languageEnglish (US)
Pages (from-to)F163-F173
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number2
DOIs
StatePublished - Aug 1 2017

    Fingerprint

Keywords

  • Albuminuria
  • Chronic kidney disease
  • Glomerulus
  • Proximal tubule

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this