Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released within the heart during myocardial ischemia. The present study was done to determine the regional localization and abundance of CGRP receptors in the guinea pig heart. CGRP binding sites in 20 μm frozen sections of heart were labeled using [125I]CGRP. Non-specific binding was determined in the presence of 1 μM unlabeled CGRP or CGRP8-37. Significant amounts of specific CGRP binding were identified in atrial and ventricular myocardium, all portions of the conducting system, coronary arteries, the aorta and pulmonary trunk and intracardiac ganglia. Specific binding of CGRP to the left atrium was two-fold higher than binding to the right atrium (0.667±0.052 v 0.340 ± 0.029 fmol/mg tissue, n = 5, CGRPs8-37 group). In contrast to the atria, a lower and uniform density of CGRP receptors occurred in contractile tissue of the ventricular myocardium (e.g. 0.239 ± 0.013 fmol/mg left ventricle, n = 5). The highest concentration of CGRP receptors in guinea pig cardiac tissue occurred at the bundle of His and the bundle branches (0.752 ± 0.087 and 0.71.3 ± 0.138 fmol/mg tissue, respectively, n = 5). CGRP receptors were localized to coronary vessels throughout the heart and to the ascending aorta and pulmonary trunk. Lastly, intracardiac ganglia exhibited moderate levels of specific [125I]CGRP binding (0.475 ± 0.043 fmol/mg, n = 5). These findings support the concept that CGRP can have direct effects on atrial and ventricular function as well as coronary flow. The high density of CGRP receptors in the distal conducting system and the presence of CGRP receptors in intracardiac ganglia further suggest that CGRP could have important effects on cardiac conduction velocity and parasympathetic regulation of the heart.

Made available in DSpace on 2016-06-02T20:19:23Z (GMT). No. of bitstreams: 1 5772.pdf: 2838907 bytes, checksum: dd99c753250191bec4e2415172771de9 (MD5) Previous issue date: 2014-02-24 / Financiadora de Estudos e Projetos / Background: Muscle changes of paretic limb resulting from stroke lead to changes in the mechanical properties of muscles, such as muscle weakness and increased resistance to stretching. Studies that characterize the components of the muscle tissue, as the noncontractile, and biomarkers related to proliferation of connective tissue (such as TGF-&#946;1 and myostatin) are clinically relevant and necessary for understanding of the resistance to stretching of paretic muscles. Therefore, the aim of this study was to evaluate the serum concentration of TGF-&#946;1 and myostatin, the percentage volume of non-contractile tissue and passive peak torque and resistance to stretching (stiffness) of the extensor and flexor muscles of the knee in chronic hemiparesis. Methods: Cross-sectional study. Fourteen subjects with chronic hemiparesis post stroke and fourteen healthy paired-subjects participated in this study. Paretic, non-paretic and control limbs were evaluated. MRI images were obtained in all subjects and the percentage volume of non-contractile tissue of the quadriceps and hamstrings was measured. Serum TGF-&#946;1 and myostatin concentrations were quantified by ELISA method. Passive torque peak and resistance during stretching (stiffness) of extensors and flexors muscles of knee were assessed at 60°/s using isokinetic dynamometer. Results: An increase in the percentage volume of non-contractile tissue in VM and VL of paretic limb compared to non-paretic limb was observed (p<0,05). Also, an increase was observed in the percentage volume of non-contractile tissue in SS in paretic limb compared to control limb (p<0,05). No differences were observed in serum TGF-&#946;1 and myostatin concentrations in hemiparetic group compared to the control group (p> 0.05). Regarding passive torque, there was an increase in peak torque and resistance during passive stretching of extensor muscles with increasing ROM of paretic, non-paretic and control limbs (p<0,05), but no differences were found among limbs (p>0,05). In relation to flexor muscles, there was also an increase in peak torque along the ROM of the three limbs (p<0,05). However, non-paretic limb has lower values of peak torque than control and paretic limbs in lower ROM (p<0,05). Paretic limb increases resistance in a more accentuated pattern at intermediate ROM (50-40º) compared to control (p=0,02). A moderate correlation was observed between TGF-&#946;1 serum concentration and flexor peak torque of paretic limb, considering complete ROM (p=0,01; r=0,736). Conclusion: Paretic muscles, extensors and knee flexors, although they have increased noncontractile tissue, exhibit similar resistance to stretching the muscles of healthy subjects. Knee flexor muscles of the non-paretic limbs have less passive stretch resistance compared to healthy subjects without changes in non-contractile content. Furthermore, no changes in serum concentrations of TGF-&#946;1 and myostatin in chronic hemiparetic compared to healthy subjects were observed. / Contextualização: Alterações na musculatura do membro parético em decorrência do Acidente Vascular Cerebral (AVC) podem resultar em mudanças nas propriedades mecânicas da musculatura, como fraqueza muscular e aumento da resistência ao alongamento. Estudos que caracterizem os componentes do músculo, como o tecido não contrátil, e biomarcadores relacionados à proliferação de tecido conjuntivo (como TGF-&#946;1 e miostatina) são necessários e clinicamente relevantes para o entendimento da resistência ao alongamento de músculos paréticos. Portanto, o objetivo do presente estudo foi avaliar a concentração sérica de TGF-&#946;1 e miostatina, o volume percentual de tecido não contrátil e o pico de torque passivo e resistência ao alongamento ( stiffness ) dos músculos extensores e flexores do joelho de hemiparéticos crônicos. Materiais e Métodos: Estudo transversal. Quatorze sujeitos com hemiparesia crônica pós-AVC e quatorze sujeitos saudáveis pareados participaram deste estudo. Os membros parético, não parético e controle, foram avaliados. Imagens por ressonância magnética foram obtidas em todos os sujeitos e o volume percentual de tecido não contrátil dos músculos do quadríceps e dos isquiotibiais foi mensurado. As concentrações séricas de TGF-&#946;1 e miostatina foram quantificadas pelo método ELISA. O pico de torque passivo e a resistência ao alongamento passivo ( stiffness ) dos músculos extensores e flexores do joelho foram obtidos a 60°/s em dinamômetro isocinético e avaliados ao longo de intervalos de ADM. Resultados: Foi observado um aumento no volume percentual de tecido não contrátil nos músculos vasto medial (VM) e vasto lateral (VL) do membro parético comparado ao não parético (p<0,05). Ainda, houve um aumento no volume percentual de tecido não contrátil nos músculos semitendinoso e semimembranoso (SS) do membro parético comparado ao membro controle (p<0,05). Não foram observadas diferenças nas concentrações séricas de TGF-&#946;1 e miostatina entre os grupos (p>0,05). Houve um aumento no pico de torque e na resistência ao alongamento passivo extensor com o aumento da amplitude de movimento (ADM) nos membros parético, não parético e controle, sem diferenças entre os membros (p>0,05). Em relação aos flexores, também houve um aumento no pico de torque ao longo da ADM nos membros parético, não parético e controle. No entanto, o membro não parético apresenta valores de pico de torque menores que o parético e controle em amplitudes menores (p<0,05). O membro parético aumenta a resistência de forma mais acentuada em ADM intermediária (50-40º) comparado ao controle (p=0,02). Houve correlação moderada entre a concentração sérica de TGF-&#946;1 e o pico de torque flexor do membro parético, considerando-se a ADM completa (p=0,01; r=0,736). Conclusão: Músculos paréticos, extensores e flexores do joelho, apesar de possuírem aumento de tecido não contrátil, apresentam resistência ao alongamento semelhante a músculos de indivíduos saudáveis. Músculos flexores do joelho dos membros não parético apresentam menor resistência passiva ao alongamento comparado a indivíduos saudáveis, sem alterações no conteúdo não contrátil. Além disso, indivíduos hemiparéticos crônicos não apresentam alterações nas concentrações séricas de TGF-&#946;1 e miostatina comparados a indivíduos saudáveis.