Interleucina-10 inibe a quinase regulada por sinal extracelular 1 e 2 (ERK 1/2) em aorta de camundongos hipertensos pela infusão de angiotensina II

• Autor(a) principal: Bressan, Alecsander Fabricio Moreira
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFMT
• Texto Completo: http://ri.ufmt.br/handle/1/2508
• topic: Citocina imunorregulatória; Função vascular e inflamação; CNPQ::CIENCIAS DA SAUDE; Immuno-regulatory cytokine; Vascular function and inflammation

The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immuno-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. Hypothesized that IL-10 may act negatively on the ERK 1/2 pathway in vascular tissue during hypertension.The aim was to evaluate if IL-10 modulates vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockouts (IL-10-/-) mice received Ang II infusion (90 ηg/min, for 14 days) or vehicle (saline), via osmotic mini-pumps, whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min for 14 days) simultaneously, or not, with Ang II. The mean arterial pressure was measured by direct measurement technique. The plasma concentration of IL-10 was quantified by the ELISA technique. Aortic rings were mounted in a myograph and concentration-response curve to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μM, 40 minutes). Protein expression of vascular ERK 1/2 was determined by western blotting. Ang II infusion reduced plasma IL-10 levels, while exogenous IL-10 infusion restored plasma levels of this cytokine in Ang II-infused mice. Ang II infusion increased the maximal contraction response [milinewton (mN) corrected by% KCL] in both WT mice [218.9 ± 10.45 (Ang II) vs. 160.1 ± 7.78 (vehicle)]; and IL-10-/-[244.7 ± 5.50 (Ang II) vs. 202.1 ± 9.2 (vehicle)]. The concomitant infusion of IL-10 and Ang II prevented vascular hypercontractility in WT mice compared to the group infused only with Ang II (171.1 ± 5.8 vs. 218.9 ± 10.45 respectively). Inhibition of the ERK 1/2 pathway ameliorated Ang II induced hypercontractility. Activation 1/2 vascular ERK was amplified in arteries of infused Ang II IL-10-/- mice. The infusion of exogenous IL-10 was able to prevent vascular expression of total and phosphorylated ERK 1/2, induced by Ang II. Our results suggest that IL-10 negatively modulates vascular activation of ERK 1/2, preventing the actions of Ang II on vascular function during hypertension.