title: Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats.
abstract: Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100ppm) through drinking water for 90 consecutive days. Atorvastatin (10mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Thengumpallil Sasindran
authors.initials: TS
authors.lastname: Sarath
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Prashantkumar
authors.initials: P
authors.lastname: Waghe
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Soumen
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Ayyappan Harikrishna
authors.initials: AH
authors.lastname: Pillai
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Sankaran Kutty
authors.initials: SK
authors.lastname: Harikumar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Mishra
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India. Electronic address: snsarkar1911@rediffmail.com.
authors.forename: Souvendra Nath
authors.initials: SN
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism* / Q000633:toxicity; D000069059:Atorvastatin; D002374:Catalase / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D005979:Glutathione Peroxidase / Q000032:analysis; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017670:Sodium Compounds / Q000378:metabolism* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D018053:Arsenites; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D017670:Sodium Compounds; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C017947:sodium arsenite; D002784:Cholesterol; D000069059:Atorvastatin; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C515768:Cyba protein, rat
keywords: Arsenic; Atorvastatin; Blood pressure; Lipid profile; Rat; Redox signaling