title: Impairment of endothelium-dependent vasorelaxation in experimental atherosclerosis is dependent on gender.
abstract: OBJECTIVE
  Nitric oxide (NO) has been suggested to have antiatherosclerotic effects. It has also been demonstrated that there is a greater basal release of endothelium derived relaxing factor (EDRF) in female as compared to male rabbit aorta, which also might have beneficial effects in atherosclerosis. We thus sought to determine if gender influences the severity of atherosclerosis.
  
  
  METHODS
  We studied 18 female and 18 male New Zealand White rabbits that were randomly divided in two groups of 9 animals each and fed either a standard or a cholesterol diet (0.75%) for 15 weeks.
  
  
  RESULTS
  In cholesterol-fed rabbits the percentage of atherosclerotic lesions in the aorta was identical in females and males and was inversely correlated with the maximal aortic relaxation to acetylcholine as assessed in organ chamber experiments (females: P < 0.0008, males: P < 0.0002). Importantly, the cholesterol diet induced a significantly (P < 0.025) more severe impairment of maximal vasorelaxation to acetylcholine in males from 78.4 +/- 1.2% to 29.4 +/- 10.2%) compared to females (from 84.4 +/- 1.2% to 60.7 +/- 8.5%). Both male gender (P < 0.0001) and the extent of impairment of endothelium-dependent relaxation (P < 0.0002) were associated with a reduced aortic sensitivity to S-nitroso-N-acetyl-D,L-penicillamine, which releases NO into the organ bath. In contrast, the aortic sensitivity to the organic nitrates pentaerythritol tetranitrate and isosorbide 5-nitrate, which release NO after enzymatic metabolization within the smooth muscle, was not reduced.
  
  
  CONCLUSIONS
  These results suggest that the impairment of endothelium-dependent vasorelaxation induced by atherosclerosis is dependent on gender. This may be due to a greater degradation of extracellular NO in the vessel wall of males.
authors.affiliation: Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kojda
authors.forename: B
authors.initials: B
authors.lastname: Hüsgen
authors.forename: A
authors.initials: A
authors.lastname: Hacker
authors.forename: D
authors.initials: D
authors.lastname: Perings
authors.forename: E M
authors.initials: EM
authors.lastname: Schnaith
authors.forename: E
authors.initials: E
authors.lastname: Kottenberg
authors.forename: E
authors.initials: E
authors.lastname: Noack
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000503:physiopathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010417:Pentaerythritol Tetranitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D012737:Sex Factors; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002791:Cholesterol, Dietary; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; C100210:pentrinitrol; D010396:Penicillamine; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D000109:Acetylcholine