title: Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles.
abstract: OBJECTIVE
  We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch.
  
  
  METHODS
  Arteriolar diameters were measured via television microscopy during short-term (3-6days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100mg/kg/day).
  
  
  RESULTS
  ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet.
  
  
  CONCLUSIONS
  These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jlombard@mcw.edu
authors.forename: Jessica R C
authors.initials: JR
authors.lastname: Priestley
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Buelow
authors.forename: Scott T
authors.initials: ST
authors.lastname: McEwen
authors.forename: Brian D
authors.initials: BD
authors.lastname: Weinberg
authors.forename: Melanie
authors.initials: M
authors.lastname: Delaney
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Balus
authors.forename: Carlyn
authors.initials: C
authors.lastname: Hoeppner
authors.forename: Lynn
authors.initials: L
authors.lastname: Dondlinger
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000109:Acetylcholine / Q000737:chemistry; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D002216:Captopril / Q000737:chemistry; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D019806:Cromakalim / Q000737:chemistry; D004730:Endothelium, Vascular / Q000473:pathology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000737:chemistry; D005905:Glyburide / Q000737:chemistry; D016285:Iloprost / Q000737:chemistry; D008297:Male; D008647:Mesocricetus; D008853:Microscopy; D018715:Microscopy, Video; D009599:Nitroprusside / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry; D014652:Vascular Diseases / Q000473:pathology
chemical_list: D016877:Oxidants; D019806:Cromakalim; D013481:Superoxides; D000804:Angiotensin II; D009599:Nitroprusside; C026678:carboprostacyclin; D002216:Captopril; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D016285:Iloprost; D000109:Acetylcholine; D010100:Oxygen; D005905:Glyburide
keywords: ACE; ACh; ANG II; ARB; AT(1); ATP-sensitive potassium channel; Cu/Zn SOD; DHE; HS; K(ATP); L-NAME; LS; MAP; NG-nitro-l-arginine methyl ester; NO; PEG–SOD; PRA; PSS; ROS; RRM; SHR; SNP; SOD; WYK; Wistar–Kyoto rat; acetylcholine; angiotensin II; angiotensin II type 1 receptor; angiotensin converting enzyme; angiotensin receptor blocker; cGMP; copper zinc (intracellular) superoxide dismutase; cyclic guanosine monophosphate; dihydroethidium; ecSOD; extracellular superoxide dismutase; high salt (4.0% NaCl); low salt (0.4% NaCl); mean arterial pressure; nitric oxide; physiological salt solution; plasma renin activity; polyethylene glycol–superoxide dismutase; reactive oxygen species; reduced renal mass; sodium nitroprusside; spontaneously hypertensive rat; superoxide dismutase