A Morphometric analysis of the glomerular capillary wall of a new strain of genetically hypertensive mice

Rosenberg, Warren; Schlager, Gunther; Gennaro, Joseph F.

doi:10.1002/ar.1091950310

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Original characterization studies of hypertensive Schlager mice found that older hypertensive animals (43–50 weeks old) had a significantly smaller basement membrane mean width with numerous sub-epithelial focal thickenings compared to normotensive mice. There was no difference in epithelial slit pore width, however, (Rosenberg et al, 1979). This suggests that even with a longer hypertensive duration nephropathy is not severe in this model.…”

Section: Discussionmentioning

confidence: 91%

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

et al. 2019

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Patients with diabetic hypertensive nephropathy have accelerated disease progression. Diabetes and hypertension have both been associated with changes in renal catecholamines and reactive oxygen species. With a specific focus on renal catecholamines and oxidative stress we examined a combined model of hypertension and diabetes using normotensive BPN/3J and hypertensive BPH/2J Schlager mice. Induction of diabetes (5 × 55 mg/kg streptozotocin i.p.) did not change the hypertensive status of BPH/2J mice (telemetric 24 h avg. MAP, non-diabetic 131 ± 2 vs. diabetic 129 ± 1 mmHg, n.s at 9 weeks of study). Diabetes-associated albuminuria was higher in BPH/2J vs. diabetic BPN/3J (1205 + 196/-169 versus 496 + 67/-59 μg/24 h, p = 0.008). HPLC measurement of renal cortical norepinephrine and dopamine showed significantly greater levels in hypertensive mice whilst diabetes was associated with significantly lower catecholamine levels. Diabetic BPH/2J also had greater renal catecholamine levels than diabetic BPN/3J (diabetic: norepinephrine BPN/3J 40 ± 4, BPH/2J 91 ± 5, p = 0.010; dopamine: BPN/3J 2 ± 1; BPH/2J 3 ± 1 ng/mg total protein, p < 0.001 after 10 weeks of study). Diabetic BPH/2J showed greater cortical tubular immunostaining for monoamine oxidase A and cortical mitochondrial hydrogen peroxide formation was greater in both diabetic and non-diabetic BPH/2J. While cytosolic catalase activity was greater in non-diabetic BPH/2J it was significantly lower in diabetic BPH/2J (cytosolic: BPH/2J 127 ± 12 vs. 63 ± 6 nmol/min/ml, p < 0.001). We conclude that greater levels of renal norepinephrine and dopamine associated with hypertension, together with diabetes-associated compromised anti-oxidant systems, contribute to increased renal oxidative stress in diabetes and hypertension. Elevations in renal cortical catecholamines and reactive oxygen species have important therapeutic implications for hypertensive diabetic patients.

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Section: Discussionmentioning

confidence: 91%

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

et al. 2019

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“…Hypertensive BPH/2 mice have similar kidney-to-body weight ratio as BPN/3 (Schlager et al, 1979) but have fewer nephrons per kidney (Rosenberg et al, 1982). Morphometric analysis of kidneys from older BPH/2 mice showed none of the characteristic features of renal parenchymal pathology (Rosenberg et al, 1979) indicating that major morphological differences in the kidney are not likely driving the hypertension. However, the available filtration surface area in juxtamedullary glomeruli in BPH/2 mice is less than half that of BPN/3 mice while the superficial cortical glomeruli were comparable between strains (Rosenberg et al, 1982).…”

Section: Heart Vessel and Kidney Structure And Functionmentioning

confidence: 97%

“…An important phenotypic difference observed in BPH/2 mice is that their body weight is lower compared with BPN/3 mice (Rosenberg et al, 1982; Buu et al, 1987). However, hypotensive BPL/1 mice also have lower body weight than BPN/3 mice suggesting that this attribute is not likely to be associated with the hypertension (Rosenberg et al, 1979). Early studies suggested that water intake of female BPH/2 mice was 20% greater than the normotensive strain but if offered a choice, they preferred solutions of lower NaCl or KCl concentration (Bachmanov et al, 1998).…”

Section: Metabolic Abnormalities In Bph/2 Micementioning

confidence: 99%

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

et al. 2019

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It has been 45 years since Gunther Schlager used a cross breeding program in mice to develop inbred strains with high, normal, and low blood pressure (BPH/2, BPN/3, and BPL/1 respectively). Thus, it is timely to gather together the studies that have characterized and explored the mechanisms associated with the hypertension to take stock of exactly what is known and what remains to be determined. Growing evidence supports the notion that the mechanism of hypertension in BPH/2 mice is predominantly neurogenic with some of the early studies showing aberrant brain noradrenaline levels in BPH/2 compared with BPN/3. Analysis of the adrenal gland using microarray suggested an association with the activity of the sympathetic nervous system. Indeed, in support of this, there is a larger depressor response to ganglion blockade, which reduced blood pressure in BPH/2 mice to the same level as BPN/3 mice. Greater renal tyrosine hydroxylase staining and greater renal noradrenaline levels in BPH/2 mice suggest sympathetic hyperinnervation of the kidney. Renal denervation markedly reduced the blood pressure in BPH/2 but not BPN/3 mice, confirming the importance of renal sympathetic nervous activity contributing to the hypertension. Further, there is an important contribution to the hypertension from miR-181a and renal renin in this strain. BPH/2 mice also display greater neuronal activity of amygdalo-hypothalamic cardiovascular regulatory regions. Lesions of the medial nucleus of the amygdala reduced the hypertension in BPH/2 mice and abolished the strain difference in the effect of ganglion blockade, suggesting a sympathetic mechanism. Further studies suggest that aberrant GABAergic inhibition may play a role since BPH/2 mice have low GABAA receptor δ, α4 and β2 subunit mRNA expression in the hypothalamus, which are predominantly involved in promoting tonic neuronal inhibition. Allopregnanolone, an allosteric modulator of GABAA receptors, which increase the expression of these subunits in the amygdala and hypothalamus, is shown to reduce the hypertension and sympathetic nervous system contribution in BPH/2 mice. Thus far, evidence suggests that BPH/2 mice have aberrant GABAergic inhibition, which drives neuronal overactivity within amygdalo-hypothalamic brain regions. This overactivity is responsible for the greater sympathetic contribution to the hypertension in BPH/2 mice, thus making this an ideal model of neurogenic hypertension.

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“…In a previous study [18] no evidence of glomerular sclerosis such as that described by Cluirg and Grishman [7] were observed. There appeared to be no mesangial changes other than that of a decreased cell number [19] as might be expected in glomerular pathologies [6,17] nor was there evidence of amyloid [14].…”

Section: Discussionmentioning

confidence: 75%

“…As the Schlager strain of genetically hypertensive mice [21] demonstrated the presence of certain structural changes in the glomerular capillary wall of the hypertensive animals [18] along with changes in glomerular cellularity [19]. The present investigation was undertaken in order to further study in a quantitative manner various structural aspects of the kidney of the hypertensive mouse.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Structural Aspects of the Renal Glomeruli of Hypertensive Mice

Rosenberg

Palmieri

Schlager

et al. 1982

Nephron

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Kidneys of genetically hypertensive and normotensive mice were studied with respect to kidney weight, number and volume of glomeruli, and filtration surface area. The hypertensive animals have a larger kidney weight to body weight ratio and possess fewer glomeruli per kidney. The superficial cortical glomeruli of the hypertensives are slightly smaller in volume than those of the normotensives although the filtration surface area is similar. The juxtamedullary glomeruli of the hypertensives are both smaller in volume and have less filtration surface area. The possible implications of these findings in the development and/or maintenance of hypertension are discussed.

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A Morphometric analysis of the glomerular capillary wall of a new strain of genetically hypertensive mice

Cited by 6 publications

References 11 publications

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

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

Mechanisms Responsible for Genetic Hypertension in Schlager BPH/2 Mice

Quantitative Structural Aspects of the Renal Glomeruli of Hypertensive Mice

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