Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats

BACKGROUND AND OBJECTIVE: Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and restores endothelial dysfunction in hypertensive animal models. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression and activity, and reduced reactive oxygen species might be involved in the improvement of endothelial function induced by quercetin in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male SHR and Wistar-Kyoto (WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of eNOS, caveolin-1 and p47 were analysed by Western blot, eNOS activity by conversion of [H]arginine to L-[H]citrulline, and NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin. RESULTS: In SHR, quercetin reduced the increase in blood pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent vasoconstriction and aortic thromboxane B2 production. Compared to WKY, SHR showed upregulated eNOS and p47 protein expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood pressure, endothelial function or the expression or activity of the proteins analysed. CONCLUSIONS: Enhanced eNOS activity and decreased NADPH oxidase-mediated superoxide anion (O2) generation associated with reduced p47 expression appear to be essential mechanisms for the improvement of endothelial function and the antihypertensive effects of chronic quercetin.     

Short report: endemic focus of cystic echinococcosis in a coastal city of Peru

No evidence of Echinococcus granulosus infection has been described in the coastal region of Peru, with the exception of the capital city of Lima. Anecdotal evidence suggests the existence of a focus of echinococcosis in the coastal city of Chincha, located south of Lima. We conducted a preliminary epidemiologic study in Chincha, which included an ultrasound, chest radiography, and serologic survey of abattoir workers, a review of medical records from local hospitals, and examination of the intestines of stray dogs to determine the presence of canine echinococcosis. Among 25 abattoir workers examined for the presence of cystic echinococcosis, we found three (12%) subjects with echinococcal cysts. A review of medical records showed a surgical incidence of 32/100,000 for the period 1996-1998. Three of 48 dogs (6.25%) were found to be infected with E. granulosus tapeworms. This study demonstrates the existence of an undocumented endemic focus of E. granulosus previously unknown in the coastal region of Peru.     

Recovery of renal function in patients receiving haemodialysis treatment

The aim of this study was to review all cases of recovery of renal function in chronic haemodialysis patients, observed in the last ten years. During the study period, 218 chronic renal failure patients were managed on haemodialysis for a minimum of 90 days. In 17 cases (8%), it was possible to interrupt dialysis after 95 to 529 days. The probability of renal function recovery was higher in patients with chronic interstitial nephritis (P=.04) or autoimmune diseases (P=.07), as well as in those starting haemodialysis treatment at a frequency of two sessions per week (P=.02). No significant differences in age, gender, glomerular filtration rate at the beginning of haemodialysis treatment, or comorbidity rate were observed. Seven patients returned to haemodialysis treatment after a dialysis-free period of 11 +/- 7 months. Two patients died for reasons unrelated to renal failure treatment, and another patient was moved to another hospital following 35 months without dialysis. The other 14 patients are alive and 8 are dialysis-free, with a monitoring period of 13 to 106 months. The conclusion reached is that there is no reason why residual kidney function should inexorably worsen after the start of haemodialysis treatment, and that functional recovery is possible in some patients.     

Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy

Introduction and objectives

Molecular characterization of congenital heart diseases now includes the not infrequent dysmorphic Noonan syndrome. A study of 6 genes of the RAS-MAPK pathway in Spanish patients is presented: the impact of heart disease, clinical expressivity, and diagnostic yield are investigated.

Methods

The study included 643 patients (and 182 family members) diagnosed by dysmorphologists, cardiologists, and pediatric endocrinologists from 74 tertiary hospitals. Bidirectional sequencing analysis of PTPN11, SOS1, RAF1, BRAF, KRAS and HRAS focused on exons carrying recurrent mutations accounting for 80% to 95% of previously described mutations.

Results

Mutations were detected in 230 patients (91 women and 139 men) in 200 (31%) families (172 PTPN11+, 14 SOS1+, 9 RAF1+, 5 BRAF+). There was specific reference to the heart defect suffered in 156 index cases: 103 patients had shown pulmonary stenosis, 12 pulmonary stenosis with hyperthrophic cardiomyopathy, 18 hypertrophic cardiomiopathy, and 14 other cardiopathies; heart disease was absent in 9 index cases. Heart disease had not been documented in 23 of 30 family members with positive genotype and compatible clinical signs. Diagnostic yield was higher (P=.016) for samples from some centers (53%; 14/32) and even from certain professionals (64%; 9/14; P=.019). Characterization rate was 18% in patients for whom clinical data were not available. Genotyping led to a more precise diagnosis in 26 patients.

Conclusions

Most patients (94%) with a positive genotype had known congenital heart disease, 79% pulmonary stenosis and 12% hyperthrophic cardiomyopathy. Cardiopathy had not been documented in 76% of family members carrying the mutation. Molecular study is a useful tool in these syndromes but a more rigorous clinical diagnosis should be intended as well.Full English text available from:www.revespcardiol.org     

Patterns of Ethanol Intake in Preadolescent, Adolescent, and Adult Wistar Rats Under Acquisition, Maintenance, and Relapse-Like Conditions

Background: Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption/preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective. Methods: Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured. Results: During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g/kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged. Conclusions: In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment.