Curto período de exposição ao chumbo promove aumento da biodisponibilidade de óxido nítrico, via receptores AT2, e ativação de canais para K+ em aorta de ratos

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Data
2015-04-10
Autores
Pereira , Jonaina Fiorim
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Universidade Federal do Espírito Santo
Resumo
Lead has been reported as a hazard and risk factor for developing cardiovascular diseases. Indeed, previous study showed that seven days of lead exposure increased systolic blood pressure (SBP), decreased vascular reactivity and increased nitric oxide (NO) bioavailability in rat aortas Thus, the aim of this study was to evaluate the involvement of AT2 receptors in the increased bioavailability of NO and the participation of K + channels in aortas from lead-treated rats. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent doses 0.05 µg/100 g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE, 0,1 nM – 0,3 mM) without changing the vasodilator response to acetylcholine (ACh, 0.1 nM - 300 µM ) or sodium nitroprusside (SNP, 0.01 nM - 0.3 µM ). Incubation with L-NAME (100 mM) increased the vasoconstrictive response induced by phenylephrine in both groups, but this effect was greater in the aortas from the treated group. Incubation with PD 123319 (1 uM), an AT2 receptor specific inhibitor, increased the vasoconstrictor response induced by phenylephrine only in aortas from the treated group. Co-incubation PD 123319 (1 mM) and L-NAME (100 mM) increased the contractile response to phenylephrine in the arteries of both groups and this effect was similar in the aortas from the treated and untreated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 µM) or charybdotoxin (0.1 µM), the ACh-induced relaxation was more reduced in the leadtreated rats. Additionally, 4-AP and IbTX reduced more the relaxation elicited by SNP in the lead-treated rats. In addition, there was greater local release of NO in the leadtreated rats. The presence of L-NAME, and PD123319 normalized local release of NO in lead-treated rats. In summary, the present results suggest the involvement of AT2 receptors in increasing the bioavailability of NO in lead-treated rats. As a consequence the metal promoted activation channels for K + and this effect could be a compensatory mechanism against the increase in SBP.
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Palavras-chave
Lead , Vascular reactivity , Nitric oxide , potassium channels and AT2 receptors , chumbo , reatividade vascular , óxido nítrico , canais de potássio e receptores AT2
Citação
OLIVEIRA, J. F. P., Curto período de exposição ao chumbo promove aumento da biodisponibilidade de óxido nítrico, via receptores AT2, e ativação de canais para K+ em aorta de ratos. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2015.