Tratamento por 15 dias com tributilestanho diminui a reatividade vascular em anéis isolados de aorta de ratas

• Autor(a) principal: Rodrigues, Samya Mere Lima
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7992
• topic: Tributyltin; Vascular reactivity; Endothelium; Estrogen receptors; Vascular smooth muscle; Tributilestanho; Reatividade vascular; Endotélio; Músculo liso vascular; Estresse oxidativo; Estrogênio; Fisiologia; 612

The organotin compound such as tributyltin (TBT) is used in antifouling paints for marine businesses, damaging the marine ecosystem. TBT inhibits aromatase, the enzyme that converts testosterone to estrogen, causes imposex phenomenon that is the masculinization of females of marine animals. The estrogen confers protection to the cardiovascular system, acting on estrogen receptors present on endothelial and vascular smooth muscle. This study evaluated the effects of exposure to TBT for 15 days (100 ng / kg, orally) on vascular reactivity to phenylephrine (PHE) in isolated aorta rings of female Wistar rats (n = 10, 230-250 g), divided in CONT (untreated) and TBT groups. Isolated aortic rings with and without endothelium, were used to evaluate the vascular reactivity to PHE (cumulative doses 10-10 - 10-4 M). Data were expressed as mean standard error (± SEM) and analyzed by unpaired Student t test, differences were considered significant when p<0.05. The TBT animals showed a decrease in the 17 β-estradiol plasma levels CONT (47.2 ± 7 pg/mL vs. TBT: 32.3 ± 4.3* pg/mL, *p<0.05) and progesterone levels were increased compared to the CONT (4.0 ± 0.7 ng/mL TBT: 7.0 ± 1.2* ng/mL, *p<0.05). The aortic rings exhibited signs of atrophy after exposure for 15 days to TBT. (CONT: 0.46 ± 0.06 vs TBT: 0.19 ± 0.04* mm; CONT: 361.3 ± 27.8 vs TBT: 241.8 ± 11.2* μm2 × 103 , *p<0.01 respectively). TBT damaged the morphology of aortic tissue by increasing collagen deposition compared to CONT (17.2 ± 1.0 vs TBT: 24.8 ± 0.9%*,*p<0.05). The fluorescence intensity produced by the oxidation of dihidroetideo was higher in the TBT group showing an increase in production of O2- compared to CONT *p<0.01. The expression of ɑ-SMA protein were decreased in rings exposed to TBT (CONT: 1.00 ± 0.03 vs TBT: 0.67 ± 0.06*, *p<0.05). Treatment with TBT decreased the maximal response (Émax) to PHE compared to CONT (143.4 ± 6.1 vs TBT: 119.1 ± 8.5* % of contraction to KCl, *p<0.05). Removal of the endothelium promoted higher constrictor response at TBT than CONT group (152.6 ± 8.27 vs TBT: 194.7 ± 17.98* % of reduction to KCl, *p<0.05). The Émax at incubation with L-NAME was higher compared to the TBT CONT group (139.9 ± 12.15 vs TBT: 150.9 ± 6.85*, % of contraction to KCl, *p<0.05). The blocking of channels for K+ promoted a response of greater intensity in animals TBT than in CONT, evidenced by dAUC (area under the curve) (CONT: 27.35 ± 6.25 vs TBT: 72.9 ± 14.10*, % of contraction to KCl, *p<0.05). Inhibition of NADPH oxidase with apocynin reduced the contractile response to PHE in both groups, but the TBT group the reduction was greater (dAUC: CONT: -52.7 ± 5.2 vs TBT: -68.1 ± 4.5* contraction to KCl, *p<0.05). On TBT group the sensitivity (pD2) to sodium nitroprusside was higher than in the CONT group (pD2: -7.76 ± 0.00 vs TBT: -7.43 ± 0.14*, *p<0.05). The TBT group showed an increase in both sensitivity and maximal response to acetylcholine, compared to CONT (pD2: -6.07 ± 0.01 vs TBT: -5.62 ± 0.02*; Rmax: CONT: -105.3 ± 0.15 vs TBT: -99.17 ± 1.09*, *p <0.05). In conclusion, the treatment of rats for 15 days with TBT altered morphology, and reduced vascular reactivity in isolated aorta rings by mechanisms dependent on NO bioavailability, channels for K+ and increased oxidative stress rings.