Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

Crajoinas RO, Lessa LMA, Carraro-Lacroix LR, Davel APC, Pacheco BPM, Rossoni LV, Malnic G, Girardi ACC. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol 299:F872-F881, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00654.2009.-Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na(+)/H(+) exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 +/- 0.10 vs. 0.41 +/- 0.04 nmol/cm(2)xs), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 +/- 0.05 vs. 1.26 +/- 0.11 nmol/cm(2)xs). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.

The Association Between Physical Activity, Productivity, and Health Care Utilization Among Employees in Brazil

Objective: To document the relationship between physical activity, absenteeism, presenteeism, health care utilization, and morbidity among Brazilian automotive workers. Methods: Eligible employees (N = 620) completed a questionnaire. Univariate correlations, multivariate logistic regression, and Pearson`s product-moment correlation coefficient were used. Results: Work absenteeism was associated with physical activity at work (OPA) (odds ratio, [OR] = 1.63, 95% confidence interval [CI] = 1.31 to 2.02) and leisure physical activity time excluding sport (OR = 0.73, 95% CI = 0.58 to 1.00). Health care utilization was associated with OPA (OR = 1.25, 95% CI = 0.99 to 1.58) and leisure physical activity time excluding sport (OR = 0.76, 95% CI = 0.57 to 1.02). Presenteeism showed an indirect relationship with OPA (r = 0.099, P = 0.014). Referred morbidity was associated with OPA (OR = 1.3, 95% CI = 1.06 to 1.61) and sports during leisure time (OR = 0.67, 95% CI = 0.54 to 0.82). Conclusions: Physical activity components seem to have differential relationships to the studied outcomes. Associations measured indicate negative impacts of OPA on absenteeism, health care utilization, and morbidity, although overall physical activity did not show these relationships.

Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1

Crajoinas RO, Oricchio FT, Pessoa TD, Pacheco BP, Lessa LM, Malnic G, Girardi AC. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am J Physiol Renal Physiol 301: F355-F363, 2011. First published May 18, 2011; doi: 10.1152/ajprenal.00729.2010.-Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone considered a promising therapeutic agent for type 2 diabetes because it stimulates beta cell proliferation and insulin secretion in a glucose-dependent manner. Cumulative evidence supports a role for GLP-1 in modulating renal function; however, the mechanisms by which GLP-1 induces diuresis and natriuresis have not been completely established. This study aimed to define the cellular and molecular mechanisms mediating the renal effects of GLP-1. GLP-1 (1 mu g.kg(-1).min(-1)) was intravenously administered in rats for the period of 60 min. GLP-1-infused rats displayed increased urine flow, fractional excretion of sodium, potassium, and bicarbonate compared with those rats that received vehicle (1% BSA/saline). GLP-1-induced diuresis and natriuresis were also accompanied by increases in renal plasma flow and glomerular filtration rate. Real-time RT-PCR in microdissected rat nephron segments revealed that GLP-1 receptor-mRNA expression was restricted to glomerulus and proximal convoluted tubule. In rat renal proximal tubule, GLP-1 significantly reduced Na(+)/H(+) exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption via a protein kinase A (PKA)-dependent mechanism. Reduced proximal tubular bicarbonate flux rate was associated with a significant increase of NHE3 phosphorylation at the PKA consensus sites in microvillus membrane vesicles. Taken together, these data suggest that GLP-1 has diuretic and natriuretic effects that are mediated by changes in renal hemodynamics and by downregulation of NHE3 activity in the renal proximal tubule. Moreover, our findings support the view that GLP-1-based agents may have a potential therapeutic use not only as antidiabetic drugs but also in hypertension and other disorders of sodium retention.

Strength Training Preserves the Bone Mineral Density of Postmenopausal Women Without Hormone Replacement Therapy

Objective: The study was designed to evaluate the effects of strength training (ST) on the bone mineral density (BMD) of postmenopausal women without hormone replacement therapy. Method: Subjects were randomized into untrained (UN) or trained (TR) groups. The TR group exercised three ST sessions per week for 24 weeks, and body composition, muscular strength, and BMD of the lumbar spine and femur neck were evaluated. Results: Body weight, mass index, and fat percentage were lower after 24 weeks only in the TR group (p < .05). SR also improved the one repetition maximum test in 46% and 39% of upper and lower limbs, respectively. The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck (p < .05). Discussion: Results indicated that 24 weeks of ST improved body composition parameters, increased muscular strength, and preserved BMD in postmenopausal women.

Systemic and Local Inflammation in Peritoneal Dialysis: Mechanisms, Biomarkers and Effects on Outcome

Thanks to the technological development in peritoneal dialysis (PD) during the last three decades, the most important problem nowadays for the nephrologists is the maintenance of the long-term function of the peritoneal membrane. Although PD may exert an early survival benefit as compared with hemodialysis (HD), long-term PD is often associated with histopathological alterations in the peritoneal membrane that are linked to peritoneal ultrafiltration deficit and increased mortality risk. These alterations are closely related to the presence of a chronic activated (local and systemic) inflammatory response. PD itself may have other factors associated that could further modulate the inflammatory response, such as the bioincompatibility of dialysis solutions, fluid overload and changes in the body composition. Understanding the pathophysiology of inflammation in PD is essential for the adoption of adequate strategies to improve both membrane and patient survival. Copyright (C) 2009 S. Karger AG, Basel

Integration of Cortical Areas during Performance of a Catching Ball Task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop. Specific alpha absolute power changes were measured in quantitative electroencephalography (qEEG). Our hypothesis is that during the preparation of motoraction (i.e.. 2 s before the ball drops) integration occurs among the left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. We contend that in right-handers, the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy right handed subjects (13 men and 10 women), with ages varying between 25 and 40 years old (32.5 +/- 7.5), absence of mental and physical illness. The experiment consisted of a task of catching balls with the right hard in free drop. The three-way ANOVA analysis demonstrated all interaction between moment and position in left-medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode: p < 0.05). Summarizing, the experimental task enabled the observation of integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation.

Integration of cortical areas during performance of a catching ball task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop; specifically through quantitative electroencephalography (qEEG) alpha absolute power changes. Our hypothesis is that during the preparation of motor action (i.e., 2 s before ball`s drop) occurred integration among left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. This hypothesis supports a lateralization of motor function. Although we contend that in right-handers the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy subjects (13 male and 10 female), right handed, with ages varying between 25 and 40 years old (32.5 +/- 7.5), absence of mental and physical illness, right handed, and do not make use of any psychoactive or psychotropic substance at the time of the study. The experiment consisted of a task of catching balls in free drop. The three-way ANOVA analysis demonstrated an interaction between moment and position in left medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode: p < 0.001). Summarizing, through experimental task employed, it was possible to observe integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation. In this way, it established an absolute predominance of this mechanism under the left hemisphere. (C) 2008 Elsevier Ireland Ltd. All rights reserved.