Efeitos da exposição por sete dias ao acetato de chumbo sobre a reatividade vascular em anéis de aorta de ratos

• Autor(a) principal: Oliveira, Jonaina Fiorim Pereira de
• Data de Publicação: 2011
• 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/10/7955
• topic: Lead; Aortic rings; Oxide nitric; Potassium channel; Renin-angiotensin system; Reactive oxygen species; Chumbo; Reatividade vascular; Óxido nítrico; Canais para K+; Sistema renina-angiotensina; Espécies reativas de oxigênio; Canais de potássio; Fisiologia; 612

Chronic lead exposure induces hypertension in humans and animals affecting, among other actions, endothelial function. However, exposure for short periods with low lead concentrations is not explored yet. We investigated the effects of treatment with lead acetate for 7 days on vascular reactivity of aortic rings. Wistar rats were treated with lead for 7 days (1st dose 4 µg/100g, subsequent dose 0.05 µg/100g, i.m. to cover daily loss) or vehicle. Blood levels of lead at the end of treatment were 9.98 µg/dL ± 1.70 µg/dL and increased the systolic blood pressure (SBP) compared whit the control group (CT= 121 ±1.50 mmHg, n=12 vs Pb2+= 137 ± 2.36mmHg, n= 12). In aortic rings, lead reduced the maximal response but did not change sensitivity of concentration-response curves to phenylephrine (10-9–10-4 M). Acetylcholine (10- 11_3.10-4 M) or sodium nitroprusside (10-11- 3.10-4 M) induced concentrationdependent relaxations that were unchanged by lead. The endothelium removal, LNAME (100 µM) and tetraetilamonium (2 mM) incubation, increased the responses to phenylephrine, but these effects were bigger after lead treatment. Aminoguanidine (50 µM) incubation increased the response induced by phenylephrine only in leadtreated rats. Losartan (10 µM), enalapril (10 µM), apocinine (0.3 µM), SOD (150 U ml1 ) and catalase (1000 U/ml) incubation reduced the response induced by phenylephrine only in lead-treated rats. Indomethacin (10 µM) did not alter vascular reactivity in both experimental groups. The plasma activity of angiotensin converting enzyme (ACE) increased after treatment with lead. There was a significant correlation between SBP and ACE activity, and this is probably one of the possible mediators of increased blood pressure. However, the increase in SBP was accompanied by reduction in vascular reactivity to phenylephrine in aortic rings. This reduction in vascular reactivity appears to involve an increased bioavailability of NO and was accompanied by increased protein expression of the inducible nitric oxide synthase (iNOS) and of the phosphorylated endothelial nitric oxide synthase at Ser 1177 (p-eNOS), whit significant increase of the ratio (p-eNOS)/(eNOS) in aorta from lead-treated rats. There was also increase the participation of K + channels, contributing to the vascular reactivity reduction. The increased ACE activity associated with increased local release of angiotensin II could activate NADPH oxidase and consequently increase ROS production. Despite the involvement of the renin-angiotensin system and ROS in this experimental model, the vasodilatory effects of NO and the involvement of channels for K + were more expressive and contributed to the reduction of vascular reactivity to phenylephrine in aortic rings, possibly as a compensatory mechanism to the increased systolic blood pressure.