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

• Published in: Chemico-biological interactions 2015-07, Vol.237, p.104-114
• Main Authors: Waghe, Prashantkumar, Sarath, Thengumpallil Sasindran, Gupta, Priyanka, Kandasamy, Kannan, Choudhury, Soumen, Kutty, Harikumar Sankaran, Mishra, Santosh Kumar, Sarkar, Souvendra Nath
• Format: Article
• Language: English
• Subjects: Angiotensin II; Angiotensin II - blood; Angiotensin II - metabolism; Animals; Aorta - drug effects; Aorta - physiopathology; Arsenic; Arsenic - pharmacology; Blood Pressure - drug effects; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Hypertension; Hypertension - chemically induced; Hypertension - physiopathology; Male; MAP kinase signaling; NADPH Oxidases - metabolism; Peptidyl-Dipeptidase A - blood; Rats; Rats, Wistar; Reactive oxygen species; Receptor, Angiotensin, Type 1 - metabolism; Signal Transduction - drug effects; Superoxides - metabolism; Up-Regulation; Vascular dysfunction
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2015.06.014

•Examined if vasculotoxic effect of arsenic relates to altered angiotensin II action.•Arsenic enhanced AngII-induced aortic contraction & caused systemic hypertension.•Arsenic elevated plasma AngII level & upregulated aortic AT1R & Gαq/11 protein.•There were concomitant higher aortic expression & activity of Nox & ROS generation.•Exacerbation of AngII action can be a cause in arsenic-induced vascular disorder. 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 90days. 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.