title: Hypercholesterolemia blunts the oxidative stress elicited by hypertension in venules through angiotensin II type-2 receptors.
abstract: OBJECTIVE
  Hypertension and hypercholesterolemia elicit inflammatory and thrombogenic responses in the microvasculature. However, little is known about whether and how risk factor combinations alter microvascular function. We examined how the actions of HTN+HCh on the microvasculature differ from the responses elicited by either risk factor alone.
  
  
  METHODS
  Intravital microscopy was used to monitor the adhesion and emigration of leukocytes and dihydrorhodamine oxidation in cremaster muscle venules of wild type mice that were infused with angiotensin II for 2 weeks (HTN), placed on a high cholesterol diet (HCD), or both.
  
  
  RESULTS
  Either HTN or HCh alone enhanced the production of reactive oxygen species and promoted the recruitment of leukocytes in venules. However, the combination of HTN and HCh produced changes in ROS production and leukocyte recruitment that were greatly attenuated compared to HTN alone. The inhibitory effects of HCh on the AngII mediated responses were also observed in genetically-induced HCh (ApoE-deficient mice). Treating HCh+HTN mice with an antagonist to AT2r reversed the HCh-dependent protection against oxidative stress and inflammation during HTN.
  
  
  CONCLUSIONS
  These findings indicate that HCh blunts the oxidative stress and inflammatory cell recruitment elicited by hypertension in venules through a mechanism that involves AT2 receptor activation.
authors.affiliation: Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana 71130, United States.
authors.forename: Alper
authors.initials: A
authors.lastname: Yildirim
authors.affiliation: Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana 71130, United States.
authors.forename: Elena
authors.initials: E
authors.lastname: Senchenkova
authors.affiliation: Department of Molecular & Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana 71130, United States. Electronic address: dgrang@lsuhsc.edu.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000804:Angiotensin II; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014699:Venules / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II
keywords: Angiotensin II; Blood vessels; Hypercholesterolemia; Microcirculation; Neutrophils; Oxidative stress