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

Journal Article · Sun Apr 15 04:00:00 EDT 2018 · Environmental Research

DOI:https://doi.org/10.1016/J.ENVRES.2018.01.026· OSTI ID:23095671

Rizzetti, Danize A.; Silva, Taiz M. da; Escobar, Alyne G.; Piagette, Janaina; Peçanha, Franck M. ^[1]; Vassallo, Dalton V. ^[2]; Alonso, Maria J. ^[3]; Salaices, Mercedes ^[4]

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1. Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul (Brazil)
2. Cardiac Electromechanical and Vascular Reactivity Laboratory, Universidade Federal do Espírito Santo, Marechal Campos, 1468 Vitória, Espírito Santo (Brazil)
3. Department of Basic Health Sciences, Universidad Rey Juan Carlos, C/ Atenas s/n, Alcorcón (Spain)
4. Department of Pharmacology, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, Madrid (Spain)

Highlights: • Chronic exposure to Hg promotes Ang II AT-1 receptors upregulation in aorta. • Ang II AT-1 receptors activation induces vascular damage in rats exposed to Hg. • Upregulation of Ang II AT-1 receptors by Hg increases ROS and prostanoids levels. • Oxidative stress caused by Ang II AT-1 receptors activation reduces NO bioavailability. 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 HgCl{sub 2} 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 (HgCl{sub 2} im, first dose of 4.6 µg kg{sup −1} and subsequent doses of 0.07 µg kg{sup −1} day{sup −1}, and tap water by gavage); Losartan (saline im and losartan, 15 mg kg{sup −1} day{sup −1}, by gavage); Losartan-Mercury (HgCl{sub 2} im 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.

• OSTI ID: 23095671
• Journal Information: Environmental Research, Journal Name: Environmental Research Vol. 162; ISSN ENVRAL; ISSN 0013-9351
• Country of Publication: United States
• Language: English

Related Subjects

54 ENVIRONMENTAL SCIENCES
ANGIOTENSIN
ANTIOXIDANTS
AORTA
BIOLOGICAL AVAILABILITY
BLOOD PRESSURE
CHRONIC EXPOSURE
DRINKING WATER
MERCURY
MERCURY CHLORIDES
NITRIC OXIDE
OXIDATION
OXYGEN
RATS
RECEPTORS