ABSTRACT
In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac function was examined using isolated heart preparations. Echocardiography was used to confirm the results obtained with isolated heart studies. To elucidate the possible mechanisms involved in the cardiac phenotype observed in Mas(-/-) mice, whole-cell calcium currents in cardiomyocytes and the expression of collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart techniques revealed that Mas-deficient mice present a lower systolic tension (average: 1.4+/-0.09 versus 2.1+/-0.03 g in Mas(+/+) mice), +/-dT/dt, and heart rate. A significantly higher coronary vessel resistance was also observed in Mas-deficient mice. Echocardiography revealed that hearts of Mas-deficient mice showed a significantly decreased fractional shortening, posterior wall thickness in systole and left ventricle end-diastolic dimension, and a higher left ventricle end-systolic dimension. A markedly lower global ventricular function, as defined by a higher myocardial performance index, was observed. A higher delayed time to the peak of calcium current was also observed. The changes in cardiac function could be partially explained by a marked change in collagen expression to a profibrotic profile in Mas-deficient mice. These results indicate that Ang-(1-7)-Mas axis plays a key role in the maintenance of the structure and function of the heart.
Subject(s)
Heart/physiopathology , Proto-Oncogene Proteins/deficiency , Receptors, G-Protein-Coupled/deficiency , Angiotensin I/metabolism , Animals , Calcium Channels/metabolism , Collagen/metabolism , Coronary Vessels/physiopathology , Echocardiography , Electrophysiology , Heart Rate , In Vitro Techniques , Mice , Mice, Knockout , Myocardial Contraction , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Peptide Fragments/metabolism , Proto-Oncogene Mas , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Systole , Vascular Resistance , Ventricular FunctionABSTRACT
Skill in the diagnosis and management of functional disorders is essential for anyone concerned with human disease. The main principie is to distinguish between organic clinical entities and functional disorders. The pathophysiologic mechanisms that generate the symptoms of the functional disorders are imper- fectly understood. The most important etiologic factors are rela- ted to stress such as mental, emotional, or physical tension, strain, or distress. The importance of the functional disorders in gastroenterology is due to their high prevalence in almost all peoples at some time of their lives. The treatment of the func- tional disorders try to be specific but is very difficult because the pathophysiologic mechanisms involved are unclear. On the other hand, nonpharmacologic strategies by the physician can be efficients, mainly establishing a therapeutic relationship with your patient.
Habilidade em diagnosticar e lidar com desordens funcionais é essencial a qualquer um que cuide de doenças humanas. É fundamental distinguir entre entidades clínicas orgânias e distúrbios funcionais. A fisiopatologia dos distúrbios funcionais nâo é bem compreendida. Os fatores etiológicos mais importantes relacionam-se ao estresse, tais como estados de tensâo mental, emocional ou física. O tratamento farmacológico tem limitações como inespecificidade e os altos índices de efeito placebo. Por outro lado, a adoção de estratégias não farmacológicas pelo médico pode ser eficiente, principalmente esta- belecendo um relacionamento terapêutico com seu paciente.
