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.

Trophic action of sympathetic nerves reduces arterial smooth muscle Ca2+sensitivity during early post-natal development in rats

“…To the best of our knowledge, data supporting our observations only exist for h-caldesmon (Kacem et al 2006, Hachani et al 2010. The expression levels of RhoK did not differ between denervated and control arteries.…”

Renal Denervation Promotes Atherosclerosis in Hypertensive Apolipoprotein E-Deficient Mice Infused with Angiotensin II

“…A number of previous experimental studies have reported that sympathetic denervation promoted atherosclerosis at sites remote to the denervation procedure (Murphy et al, 1957; Snyder and Campbell, 1958; Kacem et al, 1997, 2006; Kacem and Sercombe, 2008; Hachani et al, 2010). Bilateral surgical lumbar sympathectomy has been reported to increase atherosclerosis severity in the thoracic and abdominal aorta, and iliac and femoral arteries in rabbits fed a high cholesterol diet (Murphy et al, 1957; Snyder and Campbell, 1958).…”

“…A number of experimental studies suggest that both chemical and surgical sympathetic denervation promote atherosclerosis (Murphy et al, 1957; Snyder and Campbell, 1958; Kacem et al, 1997, 2006; Kacem and Sercombe, 2008; Hachani et al, 2010). A recent study reported that RDN inhibited atherosclerosis formation in normotensive apolipoprotein E-deficient (ApoE −/− ) mice fed a high-fat diet (Wang et al, 2015).…”

Surgical Thoracic Sympathectomy Induces Structural and Biomechanical Remodeling of the Thoracic Aorta in a Porcine Model

“…Furthermore, there is evidence to suggest that sympathetic drive promotes and/or maintains SMC differentiation, its absence leading to dedifferentiation of ''contractile'' SMCs towards a highly ''synthetic'' phenotype [9,23,24]. Therefore, we postulate that the aortic structural remodeling observed in the present study was primarily the direct result of sympathetic nerve blockade to the aorta, independent of hemodynamic changes, with the increase in extracellular matrix proteins attributed to post-sympathectomy excessive SMC synthetic activity.…”