The Munich Wistar Frömter Rat: Proteinuria and Blood Pressure in Correlation to the Number of Superficial Glomeruli

Abstract

Rats with a high number of superficial nephrons (MWF/Ztm) also show an elevated urinary protein excretion and a high systolic blood pressure. To investigate a possible correlation between the number of superficial glomeruli and these physiological changes, MWF/Ztm rats were crossed and backcrossed to Wistar cryptorchic (WC/Ztm) animals with no superficial nephrons in order to produce genotypes with differing numbers of superficial glomeruli. In the parental strains, the F₁ hybrids and the 8 possible backcrosses, the number of superficial glomeruli, the distance of the 10 most superficial glomeruli to the renal surface, and the diameter of Bowman’s capsules were determined by morphometric analysis. The excretion of total protein, in detail low molecular weight proteins, albumin, and high molecular weight proteins were measured quantitatively in 5 males of each genotype. Systolic blood pressure was determined by a tail-cuff method in conscious rats. Means of each variate of the 12 available genotypes were linearly correlated and demonstrate a close correlation between the amount of superficial nephrons and the observed physiological changes, i.e. the more superficial the glomeruli the higher the urinary protein excretion, especially albumin, and the higher the systolic blood pressure.

Superficial Nephrons in BALB/c and C57BL/6 Mice Facilitate In Vivo Multiphoton Microscopy of the Kidney

“…One drawback, however, is that MWF rats not only have a desirable high percentage of superficially located glomeruli, they also show a reduced nephron number when compared to other commonly used strains such as Sprague Dawley or Wistar rats [17]. As a model of low nephron number, ageing MWF rats develop hypertension, progressive glomerulosclerosis, proteinuria, and, eventually, deterioration of renal function [6], [7], [17]. For reasons that are not entirely clear, the renal phenotype of MWF rats is more pronounced in male than female rats, making females more suitable for use in studies assessing the structure and function of the kidney and, more specifically, of the glomerulus [8].…”

“…Therefore, MPM imaging of the glomerulus and the JGA has primarily been performed in Munich-Wistar-Froemter (MWF) rats, a rat strain that features many superficially located glomeruli [5], [6]. However, the use of MWF rats in kidney research is problematic, because this rat strain suffers from progressive deterioration of kidney function, due to the development of proteinuria, glomerulosclerosis, and hypertension [5], [6], [7], [8], [9]. In mice, MPM imaging of superficially located glomeruli has been reported in intact BL/6 mouse kidneys, but imaging has been preferentially performed in the kidneys of young animals because the number of glomeruli close to the kidney surface decreases considerably as the organ grows [10].…”

Urinary Tract

“…The epithelial cells lining Bowman's capsule appear to have an important role in matrix deposition in glomerular injury. 29 Electron microscopic examination of the glomerulus in a number of species has shown that there is a single basement membrane in the capillary tuft with fenestrated endothelium on the side of the circulation and visceral epithelial cells on the side of the filtrate. 27 In adult laboratory animals the number and size of glomeruli are a relatively constant function of body weight.…”

In Vivo Visualization of the Antialbuminuric Effects of the Angiotensin-Converting Enzyme Inhibitor Enalapril

“…As a model of low nephron number, MWF rats gradually develop glomerulosclerosis, hypertension, and proteinuria (Remuzzi et al, 1988;Hackbarth et al, 1991). An in vivo inspection of the morphology of the glomeruli of 9-week-old MWF rats revealed no apparent abnormalities (Fig.…”

“…Because of their high number of superficial glomeruli, MWF rats are particularly suited for the investigation of glomerular function by MPM, and, similarly, by micropuncture (Hackbarth et al, 1983). For the investigation of the normal function of the glomerulus, however, only young MWF rats appear to be suitable because aged MWF rats develop hypertension, proteinuria, and glomerulosclerosis (Hackbarth et al, 1991). This pathology is most likely related to the low nephron number of this rat strain (Rothermund et al, 2011).…”