Search

Gestational protein intake restriction-induced long-lasting harmful outcomes in the offspring's organs and systems. However, few studies have focused on this event's impact on the brain's structures and neurochemical compounds. The present study investigated the effects on the amygdala neurochemical composition and neuronal structure in gestational protein-restricted male rats' offspring. Dams were maintained on isocaloric standard rodent laboratory chow with regular protein [NP, 17%] or low protein content [LP, 6%]. Total cells were quantified using the Isotropic fractionator method, Neuronal 3D reconstruction, and dendritic tree analysis using the Golgi–Cox technique. Western blot and high-performance liquid chromatography performed neurochemical studies. The gestational low-protein feeding offspring showed a significant decrease in birth weight up to day 14, associated with unaltered brain weight in youth or adult progenies. The amygdala cell numbers were unchanged, and the dendrites length and dendritic ramifications 3D analysis in LP compared to age-matched NP progeny. However, the current study shows reduced amygdala content of norepinephrine, epinephrine, and dopamine in LP progeny. These offspring observed a significant reduction in the amygdala glucocorticoid (GR) and mineralocorticoid (MR) receptor protein levels. Also corticotrophin-releasing factor (CRF) amygdala protein content was reduced in 7 and 14-day-old LP rats. The observed amygdala neurochemical changes may represent adaptation during embryonic development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition stress can alter the amygdala's neurochemical content and may contribute to known behavioral changes induced by gestational protein restriction. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The renin–angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague–Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p<0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1mg/kg, weekly) or losartan (30mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue. [Copyright &y& Elsevier]

Abstract: Background: Acute renal failure is a serious complication of human envenoming by Bothrops snakes. The ion pump Na+/K+-ATPase has an important role in renal tubule function, where it modulates sodium reabsorption and homeostasis of the extracellular compartment. Here, we investigated the morphological and functional renal alterations and changes in Na+/K+-ATPase expression and activity in rats injected with Bothrops alternatus snake venom. Methods: Male Wistar rats were injected with venom (0.8mg/kg, i.v.) and renal function was assessed 6, 24, 48 and 72h and 7days post-venom. The rats were then killed and renal Na+/K+-ATPase activity was assayed based on phosphate release from ATP; gene and protein expressions were assessed by real time PCR and immunofluorescence microscopy, respectively. Results: Venom caused lobulation of the capillary tufts, dilation of Bowman''s capsular space, F-actin disruption in Bowman''s capsule and renal tubule brush border, and deposition of collagen around glomeruli and proximal tubules that persisted seven days after envenoming. Enhanced sodium and potassium excretion, reduced proximal sodium reabsorption, and proteinuria were observed 6h post-venom, followed by a transient decrease in the glomerular filtration rate. Gene and protein expressions of the Na+/K+-ATPase α1 subunit were increased 6h post-venom, whereas Na+/K+-ATPase activity increased 6h and 24h post-venom. Conclusions: Bothrops alternatus venom caused marked morphological and functional renal alterations with enhanced Na+/K+-ATPase expression and activity in the early phase of renal damage. General significance: Enhanced Na+/K+-ATPase activity in the early hours after envenoming may attenuate the renal dysfunction associated with venom-induced damage. [Copyright &y& Elsevier]

Background. Electrophysiological studies in the mammalian kidney have identified two major classes of sensory receptors of the afferent renal nerves; chemoreceptors (CR) and mechanoreceptors (MR). The localization of calcitonin gene-related peptide (CGRP) and substance P (SP) in these renal pelvic sensory neurons provides an anatomical basis for a possible functional interaction between the two neuropeptides and SP receptor. The present study was performed to examine the possible changes in the responsiveness of renal sensory SP and CGRP receptors in rats with streptozotocin (STZ)-induced diabetes mellitus. Due to the crucial role of renal pelvic SP and CGRP receptors in the activation of renal sensory neurons by various stimuli, we examined whether the responsiveness of MR or CR activation and the dorsal root ganglia content of neuropeptides and neurokinin 1 receptors (NK1R) were altered in diabetic rats compared with non-diabetic rats.Methods. Afferent renal nerve activity (ARNA) was recorded from the peripheral portion of the cut end of one renal nerve branch placed on a bipolar silver wire electrode. T13 dorsal root ganglia (DRG) immunoreactivity was performed to NK1R, SP and CGRP.Results. The results of the current study confirmed that the stimulation of renal MR and CR elicited a renorenal reflex response, and that the renal pelvic administration of SP and CGRP increased ipsilateral ARNA and contralateral urinary sodium excretion with no changes in arterial pressure. We also found a decrease in NK1R expression followed by an increase in SP and CGRP levels in the DRG of diabetic rats. The ARNA response, produced by renal pelvic MR and CR stimulation, was found to be significantly attenuated in the STZ-induced diabetic model.Conclusions. These data may indicate a compensatory synthesis and/or abnormal axonal delivery of neurokinins from the cell body to synaptic portions of the neuron as the underlying reason for attenuated ARNA in renal sensory neurons of diabetic rats. [ABSTRACT FROM AUTHOR]

Abstract: The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Our laboratory recently showed that centrally administered insulin produced a dose-related increase in the urinary output of sodium, which was abolished by bilateral renal denervation, nitric oxide synthase inhibition and cerebroventricular streptozotocin administration in rats. Recent studies have shown that hyperinsulinemia induces subtle derangements of intracellular insulin–insulin receptor trafficking and insulin metabolism, which are associated with an impairment of insulin signaling. The long-term effect of high insulin levels on the periventricular region could alter insulin signaling, which in turn, may modify the central natriuretic and cardiovascular effects of this peptide. In order to evaluate this hypothesis, we investigated the effects of 7-day i.c.v. insulin administration on tubular handling and blood pressure in conscious, unrestrained rats and their controls, randomly assigned to one of two separate groups: (a) i.c.v. 0.15M NaCl-injected (n =7) and (b) i.c.v. 126.0ng insulin-injected rats (n =7). In the current study, there were no significant differences between the blood pressure, daily tap water intake and serum sodium, potassium, lithium and creatinine levels in control i.c.v. 0.15M NaCl-injected rats, compared with the insulin-treated group. Conversely, there was a significant decrease in the daily solid rat chow intake (Co: 16.4±3.5g vs. Ins: 10.3±2.6g, P =0.003) in 7-day long-term insulin-treated rats, compared with the control group. We confirmed that centrally administered insulin produced a substantial increase in the urinary output of Na+, Li+ and K+, and that the response was significantly enhanced in long-term i.c.v. insulin pre-treated animals, when compared with controls (fractional sodium excretion (FENa) from basal: 0.047±0.18% to Ins-treated: 0.111±0.035%, P =0.001). Additionally, we demonstrated that insulin-induced natriuresis occurred by increasing fractional proximal (FEPNa) from basal (16.8±2.6% to Ins-treated: 26.7±2.8%, P =0.001) and post-proximal sodium excretion (FEPPNa) from basal (0.37±0.03% to Ins-treated: 0.42±0.05%, P =0.043), despite a decreased Na+ filtered load and rat food intake. The current data suggest that centrally injected insulin maintain its CNS ability to amplify neuronal hypotensive and natriuretic pathways that counteract the known peripheral antinatriuretic effects of insulin. [Copyright &y& Elsevier]