Efeito agudo de baixa concentração de chumbo sobre a pressão arterial e reatividade pressórica : participação do sistema renina angiotensina, estresse oxidativo e da bomba de sódio
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Data
2011-02-24
Autores
Simões, Maylla Ronacher
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Universidade Federal do Espírito Santo
Resumo
Lead is an environmental contaminant widely used by man. Lead exposure is associated with hypertension and cardiovascular disease, but the mechanisms by which this metal promotes a toxic effect on the cardiovascular system are not fully elucidated. In this study an experimental model of acute exposure to low lead concentration was developed to evaluate the effects of this metal on arterial pressure, heart rate and pressure reactivity, as well the possible mechanisms that promotes an early activation of lead-induce hipertension. Wistar rats (280 to 350 g) were anesthetized with urethane (1.2 g/kg) and underwent surgery for catheterization of the carotid artery and jugular vein for blood pressure measurement and drug administration, respectively. AP, HR and pressure reactivity to phenylephrine (0.03 to 100 mg/Kg, bolus) were assessed before and after administration of lead (iv bolus doses of 320 mg/kg). The influence of hexamethonium (Hexa, 20 mg/kg), losartan (Los, 10 mg/Kg), enalapril (5 mg/Kg), canrenone (1 mg/Kg) and tempol (12 mg/Kg), was evaluated in the actions of this metal on the SAP, DAP, HR and pressure reactivity. The activity of plasma angiotensin converting enzyme (ACE), of cardiac Na+ -K + -ATPase (NKA), lipid peroxidation (through the release of malondialdehydeMDA in plasma) and the expression of AT1 and AT2 and α1 subunit of NKA in samples of animals exposed and not exposed to lead were measured. Lead exposure for 2 hours led to a blood lead concentration of 37 ± 1.7 mg/dL, which is below the blood concentration considered safe for exposed workers. This lead concentration promoted an increase in systolic arterial pressure (SAP) (Ct: 109 ± 3 mmHg vs Pb: 120 ± 4 mmHg) but did not cause changes in DAP and HR. There was also a reduction in sensitivity (PAS - Ct: -2.93 ± 0.08 vs. Pb: -1.58 ± 0.51 / PAD - Ct: - 3.53 ± 0.18 vs. Pb: -2.86 ± 0.20) after exposure to lead. Pretreatment with losartan, an AT1 receptor blocker or with enalapril, an ACE inhibitor, blocked the increase in systolic arterial pressure in this model promoted by lead, as well as canrenone, an NKA blocker, and tempol, a superoxide dismutase mimetic. However, hexamethonium, a ganglionic blocker, did not prevent this effect. Unlike, the reduction of the sensitivity promoted by lead was not restored by these drugs. Biochemical analysis revealed that acute exposure to lead was able to increase ACE (27 % compared to Ct) and NKA activity (125 % compared to Ct), and increased lipid peroxidation (23% compared to Ct). However, the protein expression of AT1, AT2, and the NKA α1 subunit was not different between groups. Given this, the acute exposure to low concentration of lead, increases systolic blood pressure by increasing the activity of the renin-angiotensin system, the activity of NKA and promote oxidative stress. These findings provide further evidence that lead, at low concentrations and acute exposure may trigger mechanisms of early development of hypertension and may be an environmental risk factor for cardiovascular disease.
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Chumbo , Sistema renina-angiotensina , Estresse oxidativo , NKA