Intravital Imaging of the Kidney in Salt‐Sensitive Hypertension

Abstract

Previous studies performed in rat kidneys shed light on the complexities of glomerular filtration of albumin and reabsorption at the proximal tubule (PT). It is now established that both PT reabsorption and transcytosis and glomerular filtration are responsible for determining the extent of albuminuria. Since hypertension is one of the most prevalent diseases worldwide, and is a major risk factor for developing albuminuria and renal failure, we investigated the mechanisms leading to albuminuria in the kidney of a rat model of salt‐sensitive hypertension, the Dahl SS rat. To determine the relative contributions of the glomerulus and PT to albuminuria in the SS rat, we applied the novel intravital two‐photon imaging to investigate the changes in renal function that occur during the development of salt‐sensitive hypertension (at 3, 7 and 14 days of high salt (HS) diet). Our results indicate that high amounts of albumin are filtered at the glomerulus in SS rats fed a low salt (LS) diet (GSCalb = 0.0155). Following HS diet consumption for 14 days, we observed significant elevations in blood pressure and albuminuria, increased prevalence of white blood cells (WBCs) within the kidneys (+Δ1.33 WBCs/image), and significant tubular damage as indicated by increased abundance of cast material (+Δ2.20 casts/image), compared to LS‐fed rats. We also observed a 57% increase in glomerular sieving of albumin (GSCalb = 0.0244) and a 58% reduction in PT reabsorption of albumin. Collectively, these results indicate that both the glomerulus and PT contribute to albuminuria in SS hypertensive rats.