title: Sympathectomy causes aggravated lesions and dedifferentiation in large rabbit atherosclerotic arteries without involving nitric oxide.
abstract: Previously [Histochem J 1997;29:279-286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.
authors.affiliation: Unité de Pathologies Vasculaires, Faculté des Sciences de Bizerte, Jarzouna, Tunisia.
authors.forename: Kamel
authors.initials: K
authors.lastname: Kacem
authors.forename: Christine
authors.initials: C
authors.lastname: Sercombe
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hammami
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Richard
authors.initials: R
authors.lastname: Sercombe
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D001488:Basilar Artery / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D006937:Hypercholesterolemia / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D016627:Oxidopamine; D011817:Rabbits; D013563:Sympathectomy, Chemical; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D016627:Oxidopamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine