NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats.

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx). Adult male Wistar rats following a 5/6 Nx were treated with enalapril (NxE group, 10 mg/kg/day, n = 9) or vehicle (Nx group, n = 8) for two weeks. On the 15th day after Nx, rats were anaesthetized and submitted to mean arterial pressure (MAP) determination before and after receiving two intravenous injections of saline (vehicle, n = 9) or NPCdc (0.3 µg/kg dissolved in saline, n = 18) separated by a 20-min interval. The kidneys were submitted to oxidative stress analysis. The basal MAP of the NxE group was nearly 20% lower (P < 0.05) than non-treated rats. NPCdc administration decreased the MAP in both groups; however, in the NxE group, the effects were observed only in the second injection. The peptide also decreased the NADPH oxidase activity in the renal cortex. Additionally, the hydrolysis of NPCdc by recombinant neprilysin (NEP) was monitored by mass spectrometry. NPCdc was cleaved by NEP at different peptides with an inhibition constant (Ki) of 1.5 µM, determined by a competitive assay using the NEP fluorescence resonance energy transfer (FRET) peptide substrate Abz-(d)Arg-Gly-Leu-EDDnp. Docking experiments confirmed the high affinity of NPCdc toward NEP. These findings provide new insights into the antihypertensive and antioxidant mechanism of action of NPCdc. Altogether, the results presented here suggest that NPCdc must be further studied as a potential therapy for cardiorenal syndromes.

Superimposing a high-fat diet on Schistosoma mansoni infection affects renin-angiotensin system components in the mouse kidney.

INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.

Superimposing a high-fat diet on schistosoma mansoni infection affects renin-angiotensin system components in the mouse kidney

Abstract INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.

On some physiological aspects of ethanol repercussion on neural and cardiorenal functions.

Chronic ethanol ingestion, mostly in young adults, constitutes a frequent drug-abuse situation, which is associated to a wide variety of pathological disturbance affecting a number of organs, including liver, kidney, heart, pancreas and brain. The ethanol effects are more prominent when occurring at the perinatal period of life, generating, among other disabilities, brain developmental and functional impairments, as well as the so-called "fetal alcoholic syndrome". However, low doses of ethanol, although not producing conspicuous signs of physiological impairment, may affect the developing organism, impairing the renal and cardiovascular system, among others. As a consequence of increased oxidative stress produced by ethanol intake and its subsequent oxidation, lipid peroxidation increases, enhancing reactive oxygen species formation, which is potentially injurious to the brain tissue. When occurring during gestation, lipid peroxidation may occur in the placenta, an event that would partially be responsible for fetal nutrition disturbance and consequently late physiological impairment. In this short review, data on ethanol effects on the nervous and cardiorenal structure and function are analyzed at the light of the most relevant hypotheses concerning ethanol mechanisms of action. Additionally, experimental data from the authors' laboratories are presented and discussed, focusing particular attention to the possibility of differential neural and cardiorenal ethanol effects as a function of the dose used in distinct experimental models.

Encapsulation and release characteristics of DCTN/PLGA microspheres.

In the present study, poly (D,L-lactic-co-glycolic)-acid microspheres containing trans-Dehydrocrotonin (DCTN) were prepared by the double emulsion method. The hypoglycemic activity of DCTN-loaded microspheres was monitored in normal glycemic mice after administration of a daily dose of DCTN (50 mg kg(-1) body weight) for 7 days. Spherical microspheres with two populations of particles with 3.20 +/- 0.10 and 7.60 +/- 0.70 microm mean diameter size microm were observed. The encapsulation efficiency of DCTN was 85.5 +/- 3.9%. The in vitro kinetic profile of DCTN from PLGA-microspheres was initially fast (burst effect of 19.4% at 2 h). Such a burst step was maintained until achieving 35.7+/-2.0% at 7h, followed by a gradual release of DCTN attaining a maximum drug release at 55.7 +/- 2.6% within 30 h. DCTN was able to reduce glucose levels (14.3%) of normal glycemic animals and this effect was improved by its encapsulation into microspheres (26.8%). The optimum glucose levels in the blood of animals treated with DCTN suspension and DCTN-loaded microspheres were 119.21 +/- 19.75 mg dL(-1) at day 5 and 103.08 +/- 18.88 mg dL(-1) at day 7, respectively. DCTN-loaded microspheres are thus offered as a potential delivery system for the treatment of metabolic diseases characterized by hyperglycemia.

Renal function in juvenile rats subjected to prenatal malnutrition and chronic salt overload.

Dietary sodium may contribute to hypertension and to cardiovascular and renal disease if a primary deficiency of the kidney to excrete sodium exists. In order to investigate whether chronic 1% NaCl in the drinking water changes blood pressure and renal haemodynamics in juvenile Wistar rats subjected to prenatal malnutrition, an evaluation of plasma volume, oxidative stress in the kidney, proteinuria and renal haemodynamics was carried out. Malnutrition was induced by a multideficient diet. Mean arterial pressure, renal blood flow and glomerular filtration rate (GFR) were measured using a blood pressure transducer, a flow probe and inulin clearance, respectively. Plasma volume and oxidative stress were measured by means of the Evans Blue method and by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, respectively. Urinary protein was measured by precipitation with 3% sulphosalicylic acid. It was observed that prenatally malnourished rats presented higher values of plasma volume (26%, P < 0.05), kidney TBARS (43%, P < 0.01) and blood pressure (10%, P < 0.01) when compared with the control group. However, they showed no change in renal haemodynamics or proteinuria. Neither prenatally malnourished nor control rats treated with sodium overload presented plasma volume or blood pressure values different from their respective control groups, but both groups presented elevated proteinuria (P < 0.01). The prenatally malnourished group treated with sodium overload presented higher values of kidney TBARS, GFR and filtration fraction (58, 87 and 72% higher, respectively, P < 0.01) than its respective control group. In summary, sodium overload did not exacerbate the hypertension in juvenile prenatally malnourished rats, but induced renal haemodynamic adjustments compatible with the development of renal disease.