The acute stimulation of beta-adrenoceptors (beta-AR) on the vessels induces vasodilatation through the activation of protein kinase A (PKA) and/ or synthesis and release of nitric oxide (NO). Microdomains in the plasma membrane of endothelial cells enriched in colesterol and caveolin (cav)-1, the caveolae, modulates the nitric oxide synthase (NOS) activity as well as the beta-AR activity. Previous results demonstrated that aorta from beta1-AR knockout (beta1-KO) mice showed an impairment of endothelium-dependent relaxation induced by acetylcholine (ACh), without changes on endothelium-independent relaxation to NO donor, suggesting that this artery has endothelial dysfunction. It is well known that chronic stimulation of beta-AR is associated with cardiac hypertrophy, and the treatment with non-selective beta-AR agonist, isoproterenol (ISO), induces this effect. Previous results in aorta from 7-days ISO-treated rat and mice demonstrated an exacerbated phenylephrine-induced contraction, oxidative stress and synthesis of pro-inflammatory cytokines, as well as the enhanced protein expression of endothelial and neuronal NOS (eNOS and nNOS, respectively) and cav-1, without changes in ACh-induced relaxation. These results suggested that cav-1 modulates eNOS activity. However, there are no functional studies that demonstrated this modulation as well as the beta-AR involved in this response. Moreover, the ISO-treatment improved the impaired ACh-induced relaxation observed in aorta beta1-KO mice. Taken together, these results suggested the hypothesis of the interaction among caveolae, NO synthesis and beta1-AR is associated with the effects induced by ISO treatment. Thus, the present project aim to investigate: 1) the mechanisms associated with the endothelial dysfunction observed in aorta of beta1-KO mice; and 2) the role of caveolae on the ACh-induced relaxation observed in aorta from ISO-treated mice, focusing on the role of beta1-AR.
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