Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII.

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.

Assessment of muscular strength with the modified sphygmomanometer test: what is the best method and source of outcome values?

BACKGROUND: Tests that are usually employed for the clinical assessment of muscular strength have notable disadvantages. The Modified Sphygmomanometer Test (MST) is a promising method because it is low-cost and provides objective measures. OBJECTIVES: To investigate the most adequate method and sources of outcome values for the assessment of strength with the MST. METHOD: Methodological study with 40 healthy adults (22.98 ± 2.26 years), who did not practice physical activity regularly. The strength of the flexors and extensors of the elbow and knee, the handgrip of the dominant side and anterior trunk flexors were randomly assessed with portable dynamometers and the MST (bag and cuff adaptations, and sphygmomanometer without adaptation) by a single examiner. An independent examiner read and recorded the values. The sources of the investigated outcome values were the first trial and the means of two and three trials. One-way ANOVAs and Pearson Correlation Coefficients were used for the analyses (α=0.05). RESULTS: For the MST methods applied to assess all muscular groups, similar values were found for all sources of outcome values (0.01

Assessment of muscular strength with the modified sphygmomanometer test: what is the best method and source of outcome values? / Avaliação da força muscular com o teste do esfigmomanômetro modificado: qual o melhor método e forma de operacionalização?

BACKGROUND: Tests that are usually employed for the clinical assessment of muscular strength have notable disadvantages. The Modified Sphygmomanometer Test (MST) is a promising method because it is low-cost and provides objective measures. OBJECTIVES: To investigate the most adequate method and sources of outcome values for the assessment of strength with the MST. METHOD: Methodological study with 40 healthy adults (22.98±2.26 years), who did not practice physical activity regularly. The strength of the flexors and extensors of the elbow and knee, the handgrip of the dominant side and anterior trunk flexors were randomly assessed with portable dynamometers and the MST (bag and cuff adaptations, and sphygmomanometer without adaptation) by a single examiner. An independent examiner read and recorded the values. The sources of the investigated outcome values were the first trial and the means of two and three trials. One-way ANOVAs and Pearson Correlation Coefficients were used for the analyses (α=0.05). RESULTS: For the MST methods applied to assess all muscular groups, similar values were found for all sources of outcome values (0.01<F<0.26; 0.77<p<1.00) with significant and positive correlations between the measures obtained with the dynamometers (0.51<r<0.94; p<0.003). CONCLUSIONS: All MST methods showed adequate results for the assessment of strength in healthy individuals, and after familiarization, only one trial was sufficient to provide reliable measures. The sphygmomanometer without adaptation is not time consuming, compared to the other adaptations, and showed the capability of measuring higher values of strength. The bag method was easily trained to be used and stabilized. .

CONTEXTUALIZAÇÃO: Testes comumente utilizados para a avaliação clínica da força muscular apresentam importantes desvantagens. O Teste do Esfigmomanômetro Modificado (TEM) é promissor para esse fim, por ser barato e fornecer medidas objetivas. OBJETIVOS: Investigar o método e a forma de operacionalização mais adequados para avaliação da força muscular com o TEM. MÉTODO: Estudo metodológico, com 40 adultos saudáveis (22,98±2,26 anos), não praticantes de atividade física regular. A força dos músculos flexores/extensores de cotovelo e joelho e preensores palmares do lado dominante e flexores anteriores de tronco foi avaliada com os dinamômetros portáteis e diferentes métodos do TEM (adaptações da bolsa, da braçadeira e não adaptado) por um único examinador, em ordem aleatória, com leitura e registro dos valores por outro examinador. As operacionalizações investigadas foram: primeira repetição e médias de duas e três repetições. One-way ANOVA e Coeficientes de Correlação de Pearson foram utilizados para análises (α=0,05). RESULTADOS: Para todo os métodos do TEM, utilizados para avaliar os grupos musculares, foram encontrados valores similares para todas as formas de operacionalização(0,01<F<0,26;0,77<p<1,00) e correlações significativas e positivas com as medidas dos dinamômetros(0,51<r<0,94; p<0,003). CONCLUSÕES: Estatisticamente, os diferentes métodos do TEM se mostraram igualmente adequados para avaliação da força muscular de adultos saudáveis, e apenas uma repetição, após familiarização, foi suficiente para obtenção de resultados adequados. Nenhuma demanda de tempo para realizar a adaptação ...