Tratamento com anti-TLR-3 reduz níveis pressóricos de ratos hipertensos: foco no sistema renal

Abstract

TLR-3 (Toll Like-3) is an immunological receptor that is part of the innate system and plays an important role in the viral immunity response, recognizing RNA double strands associated with PAMPs or DAMPs. When TLR-3 is activated, it triggers a signaling cascade that leads to the production of pro-inflammatory cytokines and the activation of immune cells. This inflammatory response is a key part of the body's defense against viral infections, yet it can become excessive and cause tissue damage and disease. Recent studies demonstrate that TLR3 plays an important role in the pathogenesis of arterial hypertension, as they point to hypertension as a disease related to the immune system and inflammation. The objective of this work was to evaluate the blood pressure levels of hypertensive rats after treatment with 21 days of anti-TLR-3 and also its effect on the renal system. Four groups of animals were divided, namely: Wistar IGG-normotensive rats treated with anti-IgG antibody (n=6); SHR-IgG – hypertensive rats treated with anti-IgG (n=7); Wistar TLR-3 - normotensive rats treated with anti-TLR-3 (n=7) and SHR TLR-3 - hypertensive rats treated with anti-TLR-3 (n=7). These animals were submitted to treatment with Anti-TLR-3, after which their blood pressure levels were evaluated using the caudal plethysmography technique. The levels of creatinine and serum urea were also measured in order to assess the function of the renal system. After the death of these animals, kidney samples were collected, and histology was performed in order to evaluate the renal morphology at the end of the treatment. Statistical analysis was determined by Student's t test and P values <0.05 were considered statistically significant. A reduction in blood pressure levels was observed in SHR-TLR-3 rats [99.5 ± 4.9 vs. 223.99 ± 4.39 SHR IgG (mmHg)]. The Wistar rats treated with anti-TLR-3 showed similar systolic blood pressure than the Wistar TLR-3 [155.21± 3.13 vs. 149.14± 6.3 Wistar IgG (mmHg)]. They also showed improvement in renal morphology when compared to glomerular volume distribution in the experimental groups. Mean glomerular volume shifts to the right in the SHR IgG group compared to the Wistar IgG group, with most glomeruli having a volume of approximately 700,000 vs. 600,000µ3, respectively. Treatment with anti-TLR-3 seems to generate a shift to the left, both in normotensive (500,000 µ3 Wistar TLR-3) and hypertensive (600,000 µ3 SHR TLR-3) individuals. There was no significant difference between creatinine and urea levels between groups.