Time-course morphological and functional disorders of the kidney induced by long-term high-fat diet intake in female rats.

BACKGROUND: Evidence is emerging that highlights the far-reaching consequences of a high-fat diet (HFD) on kidney morphology and function disorders. METHODS: The present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared with the appropriate gender and age-matched animals. We evaluated the kidney expression of angiotensin type II receptor and fibrotic and epithelial-to-mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical and histological techniques, in parallel with kidney function. RESULTS: In the current study, the time-course HFD-treated group showed, by immunoblotting and immunohistochemical analysis, an early time-course increase in the expression of transforming growth factor ß-1 (TGFß-1) in the entire kidney of HFD-treated rats, compared with that observed in the control group. Simultaneously, the study shows a transient increase in the expression of ZEB2 in the HFD whole kidney accompanied by a fall in the E-cadherin expression and increased collagen and fibronectin deposition. A pronounced decrease in fractional urinary sodium excretion was also demonstrated in the long-term HFD-treated rats. The decreased FENa(+) was accompanied by a fall in FEPNa(+) and FEPPNa(+), which occurred in association with significantly decreased CCr and, certainly on the sodium-filtered load. The reduction in the glomerular filtration rate (GFR) occurred in parallel to proteinuria and glomerular desmin overexpression. CONCLUSIONS: The results of the current study suggest that podocyte injury in parallel with observed proteinuria and evidence of EMT transformation are associated with long-term loss of kidney function and renal sodium and water retention.

Severe Gestational Low-Protein Intake Impacts Hippocampal Cellularity, Tau, and Amyloid-ß Levels, and Memory Performance in Male Adult Offspring: An Alzheimer-Simile Disease Model?

BACKGROUND: Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. OBJECTIVE: Considering the lack of evidence, we aimed to analyze the effects of gestational protein restriction on learning and memory function associated with hippocampal cell numbers and neurodegenerative protein content later in life. METHODS: Experiments were conducted in gestational low- (LP, 6% casein) or regular-protein (NP, 17% casein) diet intake offspring. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime were observed. RESULTS: The birthweight of LP males is significantly reduced relative to NP male progeny, and hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. The results showed an increased proximity measure in 87-week-old LP compared to NP offspring. Also, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86-wk of life. The estimated neuron number was unaltered in LP rats; however, non-neuron cell numbers increased compared to NP progeny. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, amyloid-ß peptide (Aß), and tau protein in 88-week-old LP relative to age-matched NP offspring. CONCLUSION: To date, no predicted studies showed changes in hippocampal morphological structure in maternal protein-restricted elderly offspring. The current data suggest that gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer's disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be an elegant and novel method for constructing an AD-like model in adult male offspring.

Evaluation of arterial blood pressure and renal sodium handling in a model of female rats in persistent estrus.

The aim of this study was to evaluate the arterial blood pressure and renal function of female rats in persistent estrus. Twenty-five female Wistar-Hannover rats were randomly divided into two groups: Group I (control, n = 15) and experimental (persistent estrus, n = 10). A tail-cuff system was used to measure blood pressure at 12 weeks of life. Parameters to evaluate renal function were taken into consideration. A significant increase in arterial pressure and a significant decrease in fractional sodium excretion were found in the androgenized animals compared to controls. There was no difference between the two groups with respect to glomerular filtration rate or in fractional potassium excretion. An increase in blood pressure and a reduction in fractional sodium excretion occur in female rats in persistent estrus.

Impaired dipsogenic and renal response to repetitive intracerebroventricular angiotensin II (AngII) injections in rats.

The role of the central nervous system (CNS) in the control of blood pressure and hydrosaline homeostasis has been demonstrated by several studies. While circulating angiotensin II (AngII) tends to retain sodium by a direct renal action as well as through aldosterone release, stimulation of brain AngII receptors has been reported to induce natriuresis. Repetitive intracerebroventricular AngII injection was recently demonstrated to be capable of leading to desensitisation of the dipsogenic effect of AngII stimuli. The aim of the current study was to investigate a possible central desensitisation to AngII stimuli by observing the effects of a low-concentration solution of AngII on the dipsogenic and natriuretic mechanisms in conscious rats, compared with appropriate age-matched 0.15 M NaCl-injected subjects, as evaluated by lithium clearance. The present report confirmed earlier reports on the potent natriuretic and dipsogenic effects of central AngII receptor stimulation. Natriuresis is mediated by a decrease in sodium reabsorption in the proximal and post-proximal tubule segments of the nephron. The current findings lend further support to the idea that AngII, in the CNS, is instrumental in the regulation of body fluid homeostasis. The magnitude of the dipsogenic and renal response to AngII was significantly decreased by repetitive stimulus.

Development of hypertension in a pyelonephritis-induced model: the effect of salt intake and inability of renal sodium handling.

The role of the kidney in the control of blood pressure has been convincingly demonstrated by several studies. Recent evidence has suggested that subtle acquired tubulointerstitial injury may cause a defect in sodium excretion function, thus leading to salt-sensitive hypertension. There are no reports, however, examining the effect of experimental chronic pyelonephritis on renal sodium handling and arterial pressure. Thus, to examine the influence of salt intake and unilateral nephrectomy, unanesthetized, unrestrained rats were randomly assigned to one of two separate groups: sham-operated rats (CO) or chronic unilateral pyelonephritic rats (CP). After twenty one days, the pyelonephritic group was subdivided in two: one subgroup continued with water intake (CPw), while the other was changed to 0.9% NaCl intake (CPs), like the control group (COs). After seven days, all rats were submitted to unilateral nephrectomy of the left normal kidney. Data presented herein show that chronic pyelonephritis produced an increase in mean arterial pressure (CO: 121.4 +/- 1.0 mmHg to CP: 127.0 +/- 0.9 mmHg, p = 0.000) that was enhanced by saline ingestion (COs: 121.6 +/- 1.4 mmHg; CPw: 127.0 +/- 1.8 mmHg; CPs: 132.1 +/- 1.2 mmHg, p = 0.000) and further aggravated by unilateral nephrectomy (CO: 125.2 +/- 2.6 mmHg; CPw: 127.5 +/- 0.9 mmHg; CPs: 139.2 +/- 1.1 mmHg, p = 0.000). Unchanged blood pressure measurements (120.2 +/- 2.3 mmHg) were observed beyond 21 days in control rats maintained on water regimen when compared with saline-drinking groups. These changes in mean arterial pressure were observed despite an increased fractional sodium excretion in the CPs group compared to the other groups before uninephrectomy (COs: 0.125 +/- 0.025%; CPw: 0.045 +/- 0.013%; CPs: 0.292 +/- 0.046%; p = 0.000), as compared to CPw after uninephrectomy (COs: 0.249 +/- 0.077%; CPw: 0.062 +/- 0.011%; CPs: 0.363 +/- 0.195%, p = 0.019). In addition, it was shown that daily liquid intake was higher in CPs than in CPw but similar to COs, both before uninephrectomy (COs: 42.8 +/- 2.6 ml/d; CPw: 34.3 +/- 3.5 ml/d; CPs: 51.8 +/- 3.7 ml/d, p = 0.006) and after uninephrectomy (COs: 40.9 +/- 5.5 ml/d; CPw: 33.8 +/- 1.4 ml/d; CPs: 53.0 +/- 3.5 ml/d, p = 0.004). The current data suggest that chronic pyelonephritis promotes an inability of renal tubules to handle sodium excretion when exposed to sodium overload and aggravated by uninephrectomy, thus constituting a model for salt-sensitive hypertension.