Mercury-induced vascular dysfunction is mediated by angiotensin II AT-1 receptor upregulation.

Abstract:

:Low doses of mercury (Hg) promote deleterious effects on cardiovascular system, but the mechanisms implicated remain unclear. This study analyzed whether angiotensin II AT-1 receptors are involved in the vascular dysfunction caused by chronic exposure to low HgCl2 doses. For this, rats were divided into four groups and untreated (saline by im injections and tap water by gavage) or treated for 30 days as follows: Mercury (HgCl2im, first dose of 4.6 µg kg-1 and subsequent doses of 0.07 µg kg-1 day-1, and tap water by gavage); Losartan (saline im and losartan, 15 mg kg-1 day-1, by gavage); Losartan-Mercury (HgCl2im and Losartan by gavage). Systolic blood pressure was measured by tail plethysmography, vascular reactivity in aorta by isolated organ bath, oxidative stress by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and antioxidant capacity (FRAP) and protein expression of AT-1 receptors by Western Blot. As results, co-treatment with losartan prevented the increased aortic vasoconstrictor responses to phenylephrine (Phe), the involvement of ROS and prostanoids on the response to Phe and the reduced negative endothelial modulation by nitric oxide on these responses. Moreover, this co-treatment avoided the increase in plasmatic and vascular oxidative stress and AT-1 protein expression in aorta. In conclusion, these results suggest that AT-1 receptors upregulation might play a key role in the vascular damage induced by Hg exposure by increasing oxidative stress and probably by reducing NO bioavailability.

journal_name

Environ Res

journal_title

Environmental research

authors

Rizzetti DA,da Silva TM,Escobar AG,Piagette J,Peçanha FM,Vassallo DV,Alonso MJ,Salaices M,Wiggers GA

doi

10.1016/j.envres.2018.01.026

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

287-296

eissn

0013-9351

issn

1096-0953

pii

S0013-9351(18)30025-2

journal_volume

162

pub_type

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