Navegando por Assunto "Acetylcholine"

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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.
A potential role of cholinergic dysfunction on Impaired Colon Motility in experimental intestinal Chagas disease.
(2022) Ricci, Mayra Fernanda; Béla, Samantha Ribeiro; Barbosa, Joana Lobato; Moraes, Michele Macedo; Mazzeti, Ana Lia; Bahia, Maria Terezinha; Horta, Laila Sampaio; Santiago, Helton da Costa; Cruz, Jader dos Santos; Capettini, Luciano dos Santos Aggum; Arantes, Rosa Maria Esteves
Background/Aims Chagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi-induced progressive colonic structural changes modulate the colonic contractile pattern activity. Methods We developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction. Results In the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters. Conclusions T. cruzi-induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic.
Pyridostigmine blunts the increases in myocardial oxygen demand elicited by the stimulation of the central nrvous system in anesthetized rats.
(1999) Guimarães, Andrea Grabe; Alves, Leandro Miranda; Tibiriçá, Eduardo Vera; Nobrega, Antonio Claudio Lucas da
The purpose of the present work was to verify the effect of pyridostigmine bromide, a reversible cholinesterase inhibitor, on the increases in cardiac work and myocardial oxygen demand produced by central sympathetic stimulation in pentobarbitalanesthetized Wistar rats. The pharmacological stimulation of the central nervous system with L-glutamate (1 mg/kg, intracerebroventricular) elicited marked increases in arterial pressure, dP/dtma~, rate-pressure product, and triple product, reproducing the cardiovascular alterations observed during physical effort and stressful situations. The oral administration of pyridostigmine bromide (5, 10 and 20 mg/kg) 2 hours before central stimulation blunted the increases in mean arterial pressure, dP/dt .... and triple product elicited by glutamate (29, 28 and 57% for 5 mg/kg; 26, 23 and 46% for 10 mg/kg and 19, 17 and 37% for 20 mg/kg, respectively) when compared to the control group (41, 49 and 106%, respectively; p < 0.05). Our results also showed that the activity of plasmatic cholinesterase was effectively inhibited by pyridostigmine bromide. In conclusion, the increases in endogenous acetylcholine induced by cholinesterase inhibition blunted the centrally-evoked increases in myocardial oxygen demand in anesthetized rats. This effect could represent a cardioprotective action in a situation of ischemic heart disease.