A redução no efeito máximo induzido pela BK no estômago e na aorta de animal KOB1 será melhor investigada em relação a possibilidade de haver dimerização de
receptores B2 o que também explicaria a taquifilaxia acentuada à BK nesse animal
nocaute, desde que há referência (AbdAlla e cols., 1999) que a homodimerização leva a ativação e desensibilização do receptor. Por outro lado havendo a possibilidde da formação de heterodimerização entre o receptor B2 da BK e o receptor AT1 da AII
(AbdAlla e cols., 2000) , procuraremos determinar a presença de dímeros B2 /AT1 nos
tecidos isolados de animais normais e a formação preferencial de dímeros de B2 em
tecidos de animais nocaute B1.
Quanto a ET-1, investigaremos a possível co-relação entre a concentração de ET- 1 expressa nos animais nocautes e os níveis de NO e leptina (Tanus-Santos et al., 2000), resultados esses obtidos de estudos preliminares.
Quanto a redução na capacidade relaxante do estômago isolado de animais nocaute B1, mas não de nocaute B2 quando estimulado por nitroprussiato de sódio que
age via GMP cíclico, determinaremos a concentração de Ca2+ intracelular em condições sem estímulo, nos animais nocautes comparando com a de tecidos obtidos de animais normais. Examinaremos também o papel do retículo sarcoplasmático, para verificar se há envolvimento desta organela na relagulação do Ca2+ intracelular no estômago de camundongos nocaute B1.
Quanto a aorta isolada, uma vez que afetou as respostas a BK, ET-1 e AII no animal nocaute B1, sendo os efeitos revertidos em animais nocaute B2 com relação a
responsibilidade à AII e ET-1, examinaremos com mais detalhes quais seriam os fatores envolvidos: dimerização de receptores, envolvimento de fatores tais como NO e leptina? Essas perguntas que surgiram em função dos resultados obtidos neste estudo, serão avaliadas e novos experimentos serão realizados na tentativa de esclarecer os mecanismos de ação da BK, AII e da ET-1 no músculo vascular e não-vascular.
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