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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/H1220    most recent 01232.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Damon, D. H. Search for Related Content PubMed PubMed Citation Articles by Damon, D. H.

Vascular endothelial-derived semaphorin 3 inhibits sympathetic axon growth

Department of Pharmacology, University of Vermont, Burlington, Vermont

Submitted 7 December 2004 ; accepted in final form 24 October 2005

Vascular sympathetic innervation is an important determinant of blood pressure and blood flow. The mechanisms that determine vascular sympathetic innervation are not well understood. Recent studies indicate that vascular endothelial cells (EC) express semaphorin 3A, a repulsive axon guidance cue. This suggests that EC would inhibit the growth of axons to blood vessels. The present study tests this hypothesis. RT-PCR and Western analyses confirmed that rat aortic vascular ECs expressed semaphorin 3A as well as other class 3 semaphorins (sema 3s). To determine the effects of EC-derived sema 3 on sympathetic axons, axon outgrowth was assessed in cultures of neonatal sympathetic ganglia grown for 72 h in the absence and presence of vascular EC. Nerve growth factor-induced axon growth in the presence of ECs was 50 ± 4% (P < 0.05) of growth in the absence of ECs. ECs did not inhibit axon growth in the presence of an antibody that neutralized the activity of sema 3 (P > 0.05). RT-PCR and Western analyses also indicated that sema 3s were expressed in ECs of intact arteries. To assess the function of sema 3s in arteries, sympathetic ganglia were grown in the presence of arteries for 72 h, and the percentage of axons that grew toward the artery was determined: 44 ± 4% of axons grew toward neonatal carotid arteries. Neutralization of sema 3s or removal of EC increased the percentage of axons that grew toward the artery (71 ± 8% and 72 ± 8%, respectively). These data indicate that vascular EC-derived sema 3s inhibit sympathetic axon growth and may thus be a determinant of vascular sympathetic innervation.

sympathetic nervous system; endothelium

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