Análise morfológica da musculatura cardíaca de ventrículos de camundongos com disfunção colinérgica

Abstract

Acetylcholine (ACh) is the chemical mediator of the parasympathetic nervous system and activates specific postsynaptic receptors in the heart, called muscarinic, reducing heart rate, contraction power and cellular metabolism. ACh is released into the synaptic cleft and plays its role in cardiac muscle when an important event of the cholinergic neurotransmission must happen: the NT internalization in the synaptic vesicles via vesicular ACh transporter (VAChT). Prado et al. (2006) generated a strain of mice that has reduced expression (knockdown) of VAChT gene to assess the functional importance of this transporter in cholinergic neurotransmission. Studies of cardiac abnormalities of such animals have demonstrated a decrease in cardiac function of the left ventricle with reduction of contractility index and suggestive signs of cardiac hypertrophy. This work aims to investigate possible cardiac changes in the left ventricle in VAChT WT and KD animals in the ages of 21 days, 3 and 12 months. Using optical microscopy we measured the volumetric rate of some parameters such as cellular nucleus, muscular fiber, vessels and connective tissue. Through this analysis we observed that at the histological level, there was no difference in left ventricles from animals VAChT KDHOM and WT at 21 days and 3 months. At 12 months of age, there was an increase in blood vessels profile in left ventricles from VAChT KDHOM compared to WT. We also measured the size of cardiomyocytes in the three studied ages. The animals VAChT KDHOM solely at the ages of 3 and 12 months showed a significant increase in the size of the cardiomyocytes compared to VAChT WT animals. We used transmission electron microscopy to analyze the left ventricular muscles of these animals in ultrastructural level. We measured the volumetric rate of some parameters such as mitochondria profile, myofibrils, nucleus, T tubules, among others. We observed that animals VAChT KDHOM at ages of 3 and 12 months (not 21 days) showed an increase in the number of myofibrils and a decrease in the profile of mitochondria when compared to animals VAChT WT. This data may be useful for the development of new therapeutic strategies to control aspects related to cholinergic dysfunction in aging and in diseases with impaired cardiac function.