title: Mechanisms of oxidative stress-induced increase in salt sensitivity and development of hypertension in Sprague-Dawley rats.
abstract: High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.
authors.affiliation: Heart and Kidney Institute, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors.forename: Anees Ahmad
authors.initials: AA
authors.lastname: Banday
authors.forename: Abdul Bari
authors.initials: AB
authors.lastname: Muhammad
authors.forename: Fatima Rizwan
authors.initials: FR
authors.lastname: Fazili
authors.forename: Mustafa
authors.initials: M
authors.lastname: Lokhandwala
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide