Browsing by Author "Lima, Ricardo de Freitas"

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    Antiarrhythmogenic effects of a neurotoxin from the spider Phoneutria nigriventer.
    (2011) Almeida, Alvair Pinto de; Andrade, Alexandre Barbosa; Ferreira, Anderson José; Pires, Andrea Cristina Gomes; Damasceno, Dênis Derly; Alves, Márcia Netto Magalhães; Gomes, Enéas Ricardo de Morais; Kushmerick, Christopher; Lima, Ricardo de Freitas; Prado, Marco Antônio Maximo; Prado, Vânia Ferreira; Richardson, Michael; Cordeiro, Marta do Nascimento; Guatimosim, Silvia; Gomez, Marcus Vinicius
    In this study, we evaluated the effects of PhKv, a 4584 Da peptide isolated from the spider Phoneutria nigriventer venom, in the isolated rat heart and in isolated ventricular myocytes. Ventricular arrhythmias were induced by occlusion of the left anterior descending coronary artery for 15 min followed by 30 min of reperfusion. Administration of native PhKv (240 nM) 1 min before or after reperfusion markedly reduced the duration of arrhythmias. This effect was blocked by atropine, thereby indicating the participation of muscarinic receptors in the antiarrhythmogenic effect of PhKv. Notably, recombinant PhKv (240 nM) was also efficient to attenuate the arrhythmias (3.8 0.9 vs. 8.0 1.2 arbitrary units in control group). Furthermore, PhKv induced a significant reduction in heart rate. This bradycardia was partially blunted by atropine and potentiated by pyridostigmine. To further evaluate the participation of acetylcholine on the PhKv effects, we examined the release of this neurotransmitter from neuromuscular junctions. It was found that Phkv (200 nM) significantly increased the release of acetylcholine in this preparation. Moreover, PhKv (250 nM) did not cause any significant change in action potential or Ca2þ transient parameters in isolated cardiomyocytes. Altogether, these findings show an important acetylcholine-mediated antiarrhythmogenic effect of the spider PhKv toxin in isolated hearts.
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    Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.
    (2010) Gomes, Aline Alves Lara; Damasceno, Dênis Derly; Pires, Rita Gomes Wanderley; Gros, Robert; Gomes, Enéas Ricardo de Morais; Gavioli, Mariana; Lima, Ricardo de Freitas; Guimarães, Diogo Aparecido da Silva; Lima, Patrícia Maria d'Almeida; Bueno Júnior, Carlos Roberto; Vasconcelos, Anilton Cesar; Campos, Danilo Roman; Menezes, Cristiane Alves da Silva; Sirvente, Raquel de Assis; Salemi, Vera Maria Cury; Mady, Charles; Caron, Marc G.; Ferreira, Anderson José; Brum, Patricia Chakur; Resende, Rodrigo Ribeiro; Cruz, Jader dos Santos; Gomez, Marcus Vinicius; Prado, Vânia Ferreira; Almeida, Alvair Pinto de; Prado, Marco Antônio Maximo; Fonseca, Silvia Carolina Guatimosim
    Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.