• Home
  • Search Results
  • Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling.

Arsenic causes aortic dysfunction and systemic hypertension in rats: Augmentation of angiotensin II signaling.

Chemico-biological interactions (2015-06-17)
Prashantkumar Waghe, Thengumpallil Sasindran Sarath, Priyanka Gupta, Kannan Kandasamy, Soumen Choudhury, Harikumar Sankaran Kutty, Santosh Kumar Mishra, Souvendra Nath Sarkar
ABSTRACT

The groundwater pollutant arsenic can cause various cardiovascular disorders. Angiotensin II, a potent vasoconstrictor, plays an important role in vascular dysfunction by promoting changes in endothelial function, vascular reactivity, tissue remodeling and oxidative stress. We investigated whether modulation of angiotensin II signaling and redox homeostasis could be a mechanism contributing to arsenic-induced vascular disorder. Rats were exposed to arsenic at 25, 50 and 100ppm of sodium arsenite through drinking water consecutively for 90 days. Blood pressure was recorded weekly. On the 91st day, the rats were sacrificed for blood collection and isolation of thoracic aorta. Angiotensin converting enzyme and angiotensin II levels were assessed in plasma. Aortic reactivity to angiotensin II was assessed in organ-bath system. Western blot of AT1 receptors and G protein (Gαq/11), ELISA of signal transducers of MAP kinase pathway and reactive oxygen species (ROS) generation were assessed in aorta. Arsenic caused concentration-dependent increase in systolic, diastolic and mean arterial blood pressure from the 10th, 8th and 7th week onwards, respectively. Arsenic caused concentration-dependent enhancement of the angiotensin II-induced aortic contractile response. Arsenic also caused concentration-dependent increase in the plasma levels of angiotensin II and angiotensin converting enzyme and the expression of aortic AT1 receptor and Gαq/11 proteins. Arsenic increased aortic protein kinase C activity and the concentrations of protein tyrosine kinase, extracellular signal-regulated kinase-1/2 and vascular endothelial growth factor. Further, arsenic increased aortic mRNA expression of Nox2, Nox4 and p22phox, NADPH oxidase activity and ROS generation. The results suggest that arsenic-mediated enhancement of angiotensin II signaling could be an important mechanism in the arsenic-induced vascular disorder, where ROS could augment the angiotensin II signaling through activation of MAP kinase pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Trizma® base, Primary Standard and Buffer, ≥99.9% (titration), crystalline
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
Glycine, suitable for electrophoresis, ≥99%
Sigma-Aldrich
Trizma® base, BioPerformance Certified, meets EP, USP testing specifications, suitable for cell culture, ≥99.9% (titration)
Sigma-Aldrich
Tris(hydroxymethyl)aminomethane, ACS reagent, ≥99.8%
Sigma-Aldrich
Glycine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Potassium phosphate tribasic, reagent grade, ≥98%
Sigma-Aldrich
Trizma® base, BioUltra, for molecular biology, ≥99.8% (T)
Sigma-Aldrich
Sodium (meta)arsenite, ≥90%
Sigma-Aldrich
Glycine, BioUltra, for molecular biology, ≥99.0% (NT)
Sigma-Aldrich
Sigma 7-9®, ≥99% (titration), crystalline
Sigma-Aldrich
Glycine, ACS reagent, ≥98.5%
Sigma-Aldrich
Trizma® base, ≥99.0% (T)
Sigma-Aldrich
Glycine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, ≥98.5%
Sigma-Aldrich
Tromethamine, meets USP testing specifications
Sigma-Aldrich
Trizma® base, BioXtra, pH 10.5-12.0 (1 M in H2O), ≥99.9% (titration)
SAFC
Glycine
Sigma-Aldrich
Glycine, BioXtra, ≥99% (titration)
Sigma-Aldrich
Trizma® base, ≥99.9% (titration), crystalline
Sigma-Aldrich
Trizma® base, puriss. p.a., ≥99.7% (T)
Sigma-Aldrich
Trizma® base, anhydrous, free-flowing, Redi-Dri, ≥99.9%
Sigma-Aldrich
Glycine, 99%, FCC
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
DL-Tyrosine, 99%
Sigma-Aldrich
Methanol, NMR reference standard
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
SAFC
Tromethamine
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.