Glomerular Filtration and Fluid Balance in Genetically Hypertensive Mice

Abstract

The Schlager genetically hypertensive mouse has been shown to be a valuable animal model with which to study human essential hypertension. Previous studies have characterized renal morphology, juxtaglomerular index, hematocrit, prostaglandin levels, brain catecholamines, social behavior, and patterns of inheritance. The present study continues the phenotypic characterization of this animal model. Using desiccation, isotope dilution, and clearance, the total body water, extracellular fluid volume, and glomerular filtration rate (GFR) in hypertensive and normotensive animals during normal postnatal development were measured. Additionally, using an electron microscopic tracer, the relative permeabilities of the glomerular filter in these animals were assessed. The data indicate a volume expansion in the young hypertensive animals along with a reduction in GFR. As the animals mature the volume expansion in the hypertensives subsides and is eventually reversed resulting in a lower than normal fluid volume level. The significance of the reduced GFR in the hypertensives is also diminished with age although not to the same degree as that of the fluid volume, The indication of a reduced glomerular permeability may account for the above in light of Guyton's cascade hypothesis.

Diabetes and Hypertension Differentially Affect Renal Catecholamines and Renal Reactive Oxygen Species

“…Genetic drift could be expected between this initial study and the present time, however, it is interesting to note that in this case kidney size is not necessarily linked to hypertensive status. Older studies comparing non-diabetic Schlager mouse strains also found that by 10–20 weeks of age hypertensive mice have less body fluid (as a percentage of body weight) than normotensive Schlager mice (Rosenberg et al, 1985). In the present study we found no significant differences between strains (with and without concomitant diabetes) for water intake or urine output at 18 weeks of age (Table 1).…”

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

“…Glomerular number then plateaus in BPH/2 mice, which have markedly fewer glomeruli in adulthood compared with BPN/3 mice. Total body water, used as a measure of volume expansion, was also greater in younger BPH/2 mice than BPN/3 but this trend reversed with age and resulted in a lower total body water in older mice (Rosenberg et al, 1985). When a comparison is made between glomerular number and total body volume, it is noticeable that total body volume only starts to decrease toward normal levels after glomerular number becomes lower in the BPH/2 mice.…”

“…It is also possible that renal sympathetic hyperinnervation and increased AngII levels result in increased anti-natriuretic effects in BPH/2 mice. Rosenberg and colleagues measured glomerular filtration rate in mature BPH/2 mice and while it tended to be lower than in BPN/3 mice, this did not reach significance (Rosenberg et al, 1985). Furthermore, BPH/2 mice are reportedly not salt sensitive (Leckie, 2001).…”

“…Theoretically, reduced filtration surface and permeability could lead to decreased glomerular filtration rate, volume expansion, and hypertension (Rosenberg, 1983). However, glomerular filtration rate was shown to be less in juvenile BPH/2 mice than in mature BPH/2 mice (Rosenberg et al, 1985). Yet, both normotensive and hypertensive mice have comparable glomerular number until about 7 weeks of age.…”