title: Endothelial derived vasorelaxation is impaired in human APO A-I transgenic rabbits.
abstract: Endothelium-derived relaxing factor (nitric oxide: NO) may provide an endogenous defence against atherosclerosis which impairs endothelium-dependent vascular relaxation. Atherosclerosis development is inhibited in cholesterol fed human apo A-I transgenic rabbits (Duverger, N., Circulation, 1996, 94, 713-717). We investigated if endothelium-dependent vascular relaxation is modified in human apo A-I transgenic rabbits by testing in vitro endothelium-dependent receptor-dependent vascular relaxation to acetylcholine and endothelium-dependent receptor-independent vascular relaxation to A23187 of abdominal aorta, precontracted with phenylephrine, in human apo A-I transgenic rabbits (n=4) versus non transgenic littermates (n=4). Endothelium-independent vascular relaxation was investigated with sodium nitroprusside. Vascular precontraction to phenylephrine was significantly increased in human apo A-I transgenic rabbits (p<0.05) while endothelium-independent vascular relaxation to nitroprusside was similar between human apo A-I transgenic rabbits and control rabbits. Endothelium-dependent receptor-dependent and receptor-independent vascular relaxations were reduced in human apo A-I transgenic rabbits (p<0.05). Maximum endothelium-dependent receptor-dependent vascular relaxation was negatively correlated with HDL-cholesterol and total apo A-I (rabbit+ human) plasma levels (r=0.87 and 0.86, p=0.01, respectively) but not with atherogenic plasma lipid (VLDL-cholesterol, LDL-cholesterol, VLDL+LDL cholesterol, triglycerides, apolipoprotein B) levels. These results suggest that the transgenesis of human apo A-I in rabbits impairs signal transduction of endothelial NO synthesis.
authors.affiliation: Faculty of Medicine, University of Lille II, Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Lebuffe
authors.forename: A
authors.initials: A
authors.lastname: Boullier
authors.forename: A
authors.initials: A
authors.lastname: Tailleux
authors.forename: B
authors.initials: B
authors.lastname: Delfly
authors.forename: B
authors.initials: B
authors.lastname: Dupuis
authors.forename: J C
authors.initials: JC
authors.lastname: Fruchart
authors.forename: N
authors.initials: N
authors.lastname: Duverger
authors.forename: F
authors.initials: F
authors.lastname: Emmanuel
authors.forename: P
authors.initials: P
authors.lastname: Denefle
authors.forename: B
authors.initials: B
authors.lastname: Vallet
authors.forename: P
authors.initials: P
authors.lastname: Duriez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics*; D000001:Calcimycin / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation
chemical_list: D016632:Apolipoprotein A-I; D008074:Lipoproteins; D014280:Triglycerides; D010656:Phenylephrine; D000001:Calcimycin; D002784:Cholesterol; D000109:Acetylcholine