title: Sex-specific effects of heme oxygenase-2 deficiency on renovascular hypertension.
abstract: BACKGROUND
  Heme oxygenase-2 (HO-2) is the main isoform responsible for the breakdown of heme and release of carbon monoxide in the vasculature. Vascular-derived carbon monoxide protects against excessive vasoconstriction due to agents such as angiotensin II (Ang II) and in states of deficiency of nitric oxide. The current study was designed to determine the role of HO-2 in the development of renovascular hypertension using HO-2 knockout mice.
  
  
  METHODS
  Polyurethane cuffs were placed around the left renal artery of male and female HO-2 wild-type (WT), heterozygous (HET), and knockout (KO) mice between 16 and 24 weeks of age to induce renovascular hypertension. After 3 weeks, blood pressure was measured for 5 days, after which time both clipped and unclipped kidneys were harvested.
  
  
  RESULTS
  No differences were observed in the blood pressure of sham mice between the different genotypes of both sexes. Cuffing of the left renal artery resulted in a significant increase in blood pressure in all genotypes of both sexes. In male mice, the increase in blood pressure was significantly greater in HET and KO mice as compared to WT mice (P < .05). This effect was not observed in female mice. Renovascular hypertension resulted in a significant increase (P < .05) in cardiac hypertrophy in male mice, which was not different between the genotypes. In female mice, HET and KO mice exhibited significantly greater (P < .05) cardiac hypertrophy as compared with WT mice.
  
  
  CONCLUSIONS
  These results demonstrate a sex-specific effect of HO-2 deficiency on the development of renovascular hypertension and its effects on the heart in response to the increase in blood pressure.
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St, Jackson, Mississippi.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Stout
authors.forename: Monette U
authors.initials: MU
authors.lastname: Gousset
authors.forename: Heather A
authors.initials: HA
authors.lastname: Drummond
authors.forename: Will
authors.initials: W
authors.lastname: Gray
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Pruett
authors.forename: David E
authors.initials: DE
authors.lastname: Stec
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000235:genetics*; D002248:Carbon Monoxide / Q000097:blood; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000276:immunology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency / Q000235:genetics*; D006579:Heterozygote; D006977:Hypertension, Renal / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics / Q000276:immunology; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000804:Angiotensin II; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D012083:Renin; D001663:Bilirubin
keywords: Angiotensin II; bilirubin; blood pressure; carbon monoxide; renin