N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study

The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n=1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n=795), ACE 90+ (65/90) (n=186), and ACE 90− (65/190) (n=169) based on the presence (+) or absence (−) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease

Using Precisely Defined in vivo Microbiotas to Understand Microbial Regulation of IgE.

Early life exposure to microbes plays an important role in immune system development. Germ-free mice, or mice colonized with a low-diversity microbiota, exhibit high serum IgE levels. An increase in microbial richness, providing it occurs in a critical developmental window early in life, leads to inhibition of this hygiene-induced IgE. However, whether this inhibition is dependent solely on certain microbial species, or is an additive effect of microbial richness, remains to be determined. Here we report that mice colonized with a combination of bacterial species with specific characteristics is required to inhibit IgE levels. These defined characteristics include the presence in early life, acetate production and immunogenicity reflected by induction of IgA. Suppression of IgE did not correlate with production of the short chain fatty acids propionate and butyrate, or induction of peripherally induced Tregs in mucosal tissues. Thus, inhibition of IgE induction can be mediated by specific microbes and their associated metabolic pathways and immunogenic properties

90-kDa N-domain angiotensin I-converting enzyme (ACE): possible marker for hypertension in a renal transplant model

Abstract Introduction: Hypertension is nearly universal in kidney transplant and several factors are associated with post transplant hypertension, including immunosuppressive medications and genetic predisposition. Objective: The aims were to evaluate the effects of spontaneously hypertensive rats (SHR) kidney transplantation in Wistar rats and the possible transference of 80/90-kDa N-domain ACE. Methods: To do so, the data from Wistar recipients of kidney from SHR were compared to data from transplanted Wistar submitted to CsA treatment and, to Wistar Sham. Results and Discussion: Despite the unaltered blood pressure observed at early stages, 80/90-kDa ACE was found expressed in the urine of rats 7 and 15 days after transplantation, which was intense when rats became hypertensive 30 days post-surgery. Conclusion: Our data show that this enzyme is associated with the development of hypertension, and this marker appears in the urine before any substantial blood pressure alteration

Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?

Preeclampsia (PE), one of the leading gestational hypertensive diseases, is characterized by increased blood pressure (>= 140/90 mm Hg) and pathological proteinuria after 20 weeks gestation. It is a complex, multifactorial syndrome with an unestablished etiology and cure. the search continues for a biomarker that could assist in the early prediction or diagnosis of PE, reducing the rate of maternal and fetal mortality. Based on the findings of Casarini et al. that suggest the 90 kDa isoform of the Angiotensin Converting Enzyme (ACE) as a possible marker of hypertension, we hypothesized that this isoform may be present in pregnant women with PE, since they present a transient and spontaneous model of systemic arterial hypertension in pregnancy.We believe, therefore, that pregnant women with pure PE (PPE) express the ACE 90 kDa isoform in urine, as well as having elevated isoform enzymatic activity, during pregnancy only. Postpartum, with the normalization of blood pressure, the protein isoform would no longer be expressed. Pregnant women with superimposed preeclampsia (SPE) would present the ACE 90 kDa isoform both during and after the gestation period, and its enzymatic activity would remain high as they are chronically hypertensive. It is expected that normotensive pregnant women do not present this isoform in their urine as elevated blood pressure levels do not occur. Both normotensive and PPE affected pregnant women with a family history of hypertension, will possibly express the ACE 90 kDa isoform before pregnancy and may become hypertensive, only after some years, through the influence of environmental factors and/or other diseases.If our hypothesis is confirmed, it will allow differentiation of PPE and SPE sooner than 12 weeks postpartum, which is currently the estimated period for confirmation of the specific diagnosis. Furthermore, it could be an early biomarker for predicting the disease, enabling the physician to choose the best clinical management. in addition, it would minimize the use of other methods as the biological sample for obtaining the marker is urine, a practical and effective test with good reproducibility. Finally, test results would enable a greater understanding of the mechanisms involved in gestational hypertension. (C) 2014 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS)Pontificia Univ Catolica Rio Grande do Sul, Sao Lucas Hosp, Grad Program Med & Hlth Sci Nephrol, Sch Med,Inst Biomed Res, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Med, Div Nephrol, São Paulo, BrazilWeb of Scienc

Cecropia pachystachya extract attenuated the renal lesion in 5/6 nephrectomized rats by reducing inflammation and renal arginase activity

Ethnopharmacological relevance: the plant Cecropia pachystachya Trecul has been used in Brazilian folk medicine to treat hypertension, bladder and kidney inflammation and renal diseases. the aim of this study was to evaluate the potential of the aqueous fraction from the ethanolic extract of Cecropia pachystachya (FCP) in the management of hypertension, inflammation and progressive renal disease in rats submitted to 5/6 nephrectomy.Materials and methods: Thirty male Wistar rats submitted to 5/6 nephrectomy (5/6 NE) were untreated (NE) or treated (NE+FCP) with the FCP (0.5 g/kg/day). the treatment started 15 days after surgery, and the rats were followed for a period of 60 days. Systolic blood pressure (SBP) and albuminuria were evaluated from 15-60 days after the surgical procedure. Function and estructural renal changes, TGF-beta (transforming growth factor beta), MCP-1 (monocyte chemoattractant protein-1) and nitric oxide (NO) urinary excretion were analyzed. Expression and activity of the renal enzymes arginase (ARG), angiotensin converting enzyme (ACE), and MAP kinase p-JNK expression also were analyzed.Results: the nephrectomized rats developed progressive albuminuria and increased SBP that was less intense in the treated group. There was a reduction in the glomerular filtration rate (GFR) in the nephrectomized rats, which was attenuated by treatment with FCP extract. the treatment with FCP also attenuated the histological changes, reduced the expression and activity of renal arginase, the number of macrophages (ED-1 positive cells) and the p-JNK expression in the renal cortex of the rats submitted to 5/6 NE. the urinary excretion of TGF-beta was less intense in the treated group and was associated with the reduction of the expression and activity of the renal arginase.Conclusions: These results suggest that the reduction of renal arginase activity, p-JNK and TGF-beta expression can explain the mechanism by which the treatment with C. pachystachya reduced the inflammation and improved renal function. This study presents the potential use of Cecropia pachystachya in the treatment of chronic renal diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ São Paulo, Dept Physiol, Sch Med Ribeirao Preto, São Paulo, BrazilUniv São Paulo, Dept Vet Med, Sch Anim Sci & Food Engn, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Nephrol, São Paulo, BrazilFAPESP: 11/50391-0FAPESP: 12/17059-5Web of Scienc

CHRONIC CONVENTIONAL RESISTANCE EXERCISE REDUCES BLOOD PRESSURE in STAGE 1 HYPERTENSIVE MEN

Moraes, MR, Bacurau, RFP, Casarini, DE, Jara, ZP, Ronchi, FA, Almeida, SS, Higa, EMS, Pudo, MA, Rosa, TS, Haro, AS, Barros, CC, Pesquero, JB, Wurtele, M, and Araujo, RC. Chronic conventional resistance exercise reduces blood pressure in stage 1 hypertensive men. J Strength Cond Res 26(4): 1122-1129, 2012-To investigate the antihypertensive effects of conventional resistance exercise (RE) on the blood pressure (BP) of hypertensive subjects, 15 middle-aged (46 +/- 3 years) hypertensive volunteers, deprived of antihypertensive medication (reaching 153 +/- 6/93 +/- 2 mmHg systolic/diastolic BP after a 6-week medication washout period) were submitted to a 12-week conventional RE training program (3 sets of 12 repetitions at 60% 1 repetition maximum, 3 times a week on nonconsecutive days). Blood pressure was measured in all phases of the study (washout, training, detraining). Additionally, the plasma levels of several vasodilators or vasoconstrictors that potentially could be involved with the effects of RE on BP were evaluated pre- and posttraining. Conventional RE significantly reduced systolic, diastolic, and mean BP, respectively, by an average of 16 (p < 0.001), 12 (p < 0.01), and 13 mm Hg (p < 0.01) to prehypertensive values. There were no significant changes of vasoactive factors from the kallikrein-kinin or renin-angiotensin systems. After the RE training program, the BP values remained stable during a 4-week detraining period. Taken together, this study shows for the first time that conventional moderate-intensity RE alone is able to reduce the BP of stage 1 hypertensive subjects free of antihypertensive medication. Moreover, the benefits of BP reduction achieved with RE training remained unchanged for up to 4 weeks without exercise.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Univ São Paulo, Dept Biophys, São Paulo, BrazilUniv Mogi das Cruzes, Sch Phys Educ, Mogi Das Cruzes, BrazilUniv São Paulo, Sch Arts Sci & Humanities, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniv Fed Univ São Paulo, Dept Biophys, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilFAPESP: 06/59081-6Web of Scienc