Characteristics of the actions by which 5-hydroxytryptamine affects electrical and mechanical activities in rabbit jugular vein graft

BACKGROUND AND PURPOSE The vasomodulating actions of 5-HT in vein grafts, and the underlying mechanisms, remain to be fully clarified. Here, we characterized the actions by which 5-HT affects electrical and mechanical activities in rabbit autologous jugular vein grafts. EXPERIMENTAL APPROACH Smooth muscle cell (SMC) membrane potential and isometric tension were measured in vein grafts 4 weeks after implantation into carotid arteries. Changes in the expression of 5-HT receptor subtypes and in myosin heavy chain isoforms (SM1, SM2 and SMemb) were examined by immunohistochemistry and Western blot analysis. KEY RESULTS The walls of grafted veins displayed massive increases in the number of SM1- and SM2-positive SMCs. 5-HT induced a large depolarization and contraction that were each reduced by both 5-HT2A- and 5-HT1B/1D-receptor antagonists. The 5-HT-induced contraction was not modified by a 5-HT7-receptor antagonist. The 5-HT7-receptor-selective agonist AS 19 did not induce relaxation during the contraction to prostaglandin F2a. Immunohistochemical and Western blot analyses revealed that immunoreactive responses against 5-HT2A and 5-HT1B/1D receptors were increased in the vein graft. CONCLUSIONS AND IMPLICATIONS 5-HT is able to induce a large contraction in rabbit autologous jugular vein grafts through (i) an increased number of differentiated contractile SMCs; (ii) an increased number of SMCs expressing contractile 5-HT2A- and 5-HT1B/1D receptors; and (iii) a down-regulation of the function of the relaxant SMC 5-HT7 receptors. These changes in the vein graft may help it to resist the higher pressure present on the arterial side of the circulation.