title: Low-dose angiotensin II infusion restores vascular function in cerebral arteries of high salt-fed rats by increasing copper/zinc superoxide dimutase expression.
abstract: BACKGROUND
  This study examined the vasoprotective role of circulating angiotensin II (ANG II) levels in the cerebral circulation of high salt (HS)-fed (SS.BN-(D13hmgc41-13hmgc23)/Mcwi) (Ren1-BN) congenic rats, which carry a normally functioning renin allele from the Brown Norway (BN) rat on the Dahl salt-sensitive genetic background.
  
  
  METHODS
  Ren1-BN rats were placed on an HS (4.0% NaCl) diet for 3 days. The vasodilator response to acetylcholine (ACh; 10(-10) - 10(-6) mol/L) was assessed in isolated middle cerebral arteries (MCAs), and Western blots were performed to assess the expression of the antioxidant enzymes copper (Cu)/zinc (Zn) superoxide dismutase (SOD) and manganese (Mn) SOD in cerebral resistance vessels. A separate group of HS-fed animals were infused with either a subpressor dose of ANG II (100ng/kg/min) or saline vehicle via osmotic minipump for 3 days.
  
  
  RESULTS
  HS diet eliminated acetylcholine (ACh)-induced dilation in the MCAs of the congenic rats. Western blot analysis of antioxidant enzymes showed that Cu/Zn SOD and Mn SOD expression were significantly reduced in the cerebral resistance arteries of the HS-fed rats compared with control animals fed a normal salt diet. Infusion of ANG II restored the vasodilator response to ACh in the MCAs and increased Cu/Zn SOD (but not Mn SOD) expression compared with saline-infused animals.
  
  
  CONCLUSIONS
  These results indicate that prevention of salt-induced ANG II suppression prevents vascular dysfunction in the cerebral circulation by preventing the downregulation of Cu/Zn SOD and vascular oxidant stress that normally occurs with HS diet.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Matthew J
authors: MJ
authors: Durand
authors: Julian H
authors: JH
authors: Lombard
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D003300:Copper / Q000378:metabolism*; D004195:Disease Models, Animal; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D020127:Recovery of Function; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D003300:Copper; D013482:Superoxide Dismutase
keywords: angiotensin II; antioxidant enzymes; blood pressure; cerebral circulation; endothelial dysfunction; high salt; hypertension.