Mecanismos de modulação do influxo de Ca2+ pela ativação do RyR em artérias mesentéricas de humanos e murinos

• Ano de defesa: 2018
• Autor(a) principal: Daniela Cibeli Guimaraes Garcia Lustosa
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia; UFMG
• Palavras-chave em Português: Normotensos; Hipertensos; Membrana Plasmática (MP); Retículo Sarcoplasmático (RS)
• Link de acesso: http://hdl.handle.net/1843/59197

Mechanisms involved in the excitation-contraction coupling of vascular smooth muscle (VSM) represent a complex interaction between plasma membrane (PM) and sarcoplasmic reticulum (SR). The present work investigated the PM-SR interaction involved in the contraction induced by the activation of ryanodine receptors (RyRs) in mesenteric arteries from mice and humans, normotensive and hypertensive. In vessels from normotensive mice the contraction induced by caffeine (10 mM) is partially dependent on Ca2+-influx, once in Ca2+-free solution and in the presence of SKF-96365 (30 μM), an Orai blocker, occurred reduction of contraction and Ca2+-fluorescence level. Surprisingly, blocking Cav1.2 with nifedipine (10 μM), the contraction is increased while the Ca2+-fluorescence level is reduced. Similar results were observed after blocking TRP channels with ruthenium red (RuR; 10 μM) and 2-aminoethoxydiphenyl borate (2-APB; 10 μM). Moreover, the blockage of BKCa with paxillin (1 μM) promotes increased transient contraction. Caffeine promotes hyperpolarization of VSM, which was blocked in the presence of nifedipine, 2-APB, and paxillin. In hypertensive mice the blockage of Cav1.2 and BKCa in hypertensive mice does not alter the contractile response, indicating loss of the negative feedback of the contraction. In the presence of arterial hypertension, the feedback between Cav1.2-BKCa is also impaired in humans. The present work demonstrates that the feedback between Cav1.2-BKCa is essential in mesenteric arteries. Our results indicate a new mechanism for the control of VSM contraction that may be useful for the treatment of arterial hypertension.