title: Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta.
abstract: Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca2+ ([Ca2+]i) in response to methacholine (10 microM) and histamine (10 microM) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 microM)-induced increases in [Ca2+]i were unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng x kg(-1) x min(-1) iv) for 3 days prevented impaired [Ca2+]i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on a HS diet. Adding Tempol (500 microM) to the tissue bath to scavenge superoxide anions increased NO release and caused N(omega)-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca2+ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca2+ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca2+ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca2+ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca2+ signaling, and reduced NO production in the endothelium.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Zhu
authors.forename: Ines
authors.initials: I
authors.lastname: Drenjancevic-Peric
authors.forename: Scott
authors.initials: S
authors.lastname: McEwen
authors.forename: Jill
authors.initials: J
authors.lastname: Friesema
authors.forename: Danielle
authors.initials: D
authors.lastname: Schulta
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D020013:Calcium Signaling / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013113:Spin Labels; D013481:Superoxides / Q000037:antagonists & inhibitors*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D016210:Methacholine Chloride; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D019284:Thapsigargin; D006632:Histamine; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester