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• W3048659531 endingPage "152557" @default.
• W3048659531 startingPage "152557" @default.
• W3048659531 abstract "Lead induces endothelial dysfunction and hypertension in humans and animals. Seven-day exposure to a low dose in rats reduces vasocontractile responses and increases nitric oxide (NO) bioavailability. We hypothesized that this occurs by angiotensin II receptors (AT1/AT2) activation. Wistar rats were exposed to lead acetate (1 st dose 4 μg/100 g, subsequent dose 0.05 μg/100 g/day i.m., 7 days) or saline (control group). Lead acetate exposure reduced the phenylephrine vascular response. Pre-incubations with NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) increased the contractile response in aortas from lead-treated rats. Pre-incubation with AT2 antagonist (PD123319) restored normal vascular contraction, and both PD123319 or AT1 antagonist (losartan) impeded the potentiated effects of L-NAME and wortmannin. Reinforcing those findings, increased NO bioavailability was blunted by AT1 and AT2 antagonists without summative effect when co-incubated. Finally, to test whether activation of AT1 could upregulate AT2 to increase NO bioavailability rats were simultaneously exposed to lead acetate and treated with losartan (15 mg/kg/day, orally given). Losartan prevented changes on vascular reactivity and endothelial modulation in lead-exposed group. Moreover, incubation with PD123319 had no more effects in aortic from losartan-treated rats. Our results suggest that low-dose lead acetate exposure induces an increase of NO involving mainly AT2 receptor activation and the PI3K/Protein Kinase B (PI3K/Akt) pathway. Additionally, we suggest that AT1 activation plays a role in AT2 upregulation, probably as a protective mechanism. Altogether, these effects might contribute to preserving endothelial function against the harmful effects by lead in the vascular system." @default.
• W3048659531 created "2020-08-18" @default.
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• W3048659531 date "2020-10-01" @default.
• W3048659531 modified "2023-10-17" @default.
• W3048659531 title "Increased endothelial nitric oxide production after low level lead exposure in rats involves activation of angiotensin II receptors and PI3K/Akt pathway" @default.
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• W3048659531 doi "https://doi.org/10.1016/j.tox.2020.152557" @default.
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