Relative Contributions of 5-Hydroxytryptamine (5-HT) Receptor Subtypes in 5-HT-Induced Vasoconstriction of the Distended Human Saphenous Vein as a Coronary Artery Bypass Graft

Abstract

Coronary artery bypass graft (CABG) surgery has been performed for about 40 years. In 1967, the technique of saphenous vein (SV) bypass grafting was introduced, followed 1 year later by the use of internal thoracic artery (ITA).1) Whereas ITA is the first-choice arterial graft, 2,3) SV still continues to be the most commonly used conduit vessel for CABG 4,5) because of ready availability and suppleness. One of the most serious problems in CABG surgery is that the bypass grafts often go into spasm after implantation into coronary arterial circulation, which has led to premature occlusion and increased perioperative morbidity. 6,7) Among substances that can initiate severe vasoconstriction, 5-hydroxytryptamine (5-HT) has been identified as playing an important role in the pathogenesis of vascular spasm. [8][9][10][11][12][13] Although 5-HT 2A and/or 5-HT 1B/1D receptor subtypes almost exclusively mediate 5-HT-induced vasoconstriction, [8][9][10][11][12][13][14][15][16][17][18] the relative contributions of these receptor subtypes to vasoconstrictions are species-dependent and vascular beddependent. Therefore, the selection of the best pharmacological agent to prevent 5-HT-induced spasm of the bypass grafts used in CABG surgery requires better understanding of the contributions of 5-HT receptor subtypes to vasoconstriction in the clinically used human vessels.From the viewpoint mentioned above, we revealed that 5-HT-induced vasoconstriction is mediated equivalently via 5-HT 2A and 5-HT 1B receptors in the human ITA.18) In the human SV, Borton et al. 14) have reported that both 5-HT 1 and 5-HT 2 receptors are involved in vasoconstriction by using a 5-HT 2 receptor antagonist and a 5-HT 1 receptor agonist. However, the relative contributions of 5-HT receptor subtypes that mediate vasoconstriction caused by 5-HT in the human SV are still unclear.It has been established that, before implantation into the coronary arterial circulation, the segment of SV used as a vein graft is distended by applying high intraluminal pressures with injection of saline or a patient's heparinized blood to check for leaks and to increase the vascular diameter. This fact should be considered in experiments for evaluation of 5-HT receptor subtypes responsible for vascular functions because the distension may influence both contractile and dilatory responses of the SV. 19)The aim of the present study was to elucidate the relative contribution of 5-HT receptor subtypes mediating 5-HTinduced vasoconstriction of the distended human SV obtained from CABG surgery. We examined the effects of sarpogrelate and SB224289, antagonists of 5-HT 2A and 5-HT 1B receptors, respectively, on the 5-HT-induced vasoconstriction and also performed immunolabeling of the 5-HT 2A and 5-HT 1B receptors in the distended SV. MATERIALS AND METHODS Preparation of Blood Vessels and Contractile StudiesSegments of the human SV were harvested from patients (nϭ12) who were undergoing CABG surgery at Miyazaki Prefectural Nobeoka Hospital (Miyazaki, Japan). Once the vein was comp...

5-Hydroxytryptamine Receptors as Targets for Drug Therapies of Vascular-Related Diseases

“…In fact, we observed that acetylcholine failed to induce vasodilation of the SV segments preconstricted with noradrenaline. 62) Furthermore, light and immunohistochemical microphotographs of the SV segment demonstrated that the venous wall was mainly composed of smooth muscle cells, and almost all endothelial cells were desquamated. 62) Thus, the endothelial 5-HT 1B receptor-mediated vasodilation may not occur and a selective 5-HT 1B receptor antagonist may act as merely a vasodilator in the SV graft.…”

“…62) Furthermore, light and immunohistochemical microphotographs of the SV segment demonstrated that the venous wall was mainly composed of smooth muscle cells, and almost all endothelial cells were desquamated. 62) Thus, the endothelial 5-HT 1B receptor-mediated vasodilation may not occur and a selective 5-HT 1B receptor antagonist may act as merely a vasodilator in the SV graft. In our previous study, sarpogrelate or the 5-HT 1B receptor antagonist SB224289 partially inhibited, and the combination of these antagonists almost abolished the 5-HT-induced vasoconstriction in human SVs.…”

“…In our previous study, sarpogrelate or the 5-HT 1B receptor antagonist SB224289 partially inhibited, and the combination of these antagonists almost abolished the 5-HT-induced vasoconstriction in human SVs. 62) Thus, concurrent use of 5-HT 2A and 5-HT 1B antagonists may potently prevent postoperative 5-HT-induced spasm of SV grafts in patients who have undergone CABG.…”

Upregulation of 5-Hydroxytryptamine Receptor Signaling in Coronary Arteries after Organ Culture

“…Other 5-HT receptor families are heptahelical receptors coupled to G proteins (Gs, Go, Gi, Gq/11) and have diverse effectors. 5-HT 2A and/or 5-HT 1 receptor subtypes mediate 5-HT-induced vasoconstriction exclusively [6]. The 5-HT receptors mediating constriction in coronary arteries from different species are predominantly the 5-HT 2 receptor and, to a lesser extent, 5-HT 1 receptor [1], [7].…”

Insulin Induces Internalization of the Plasma Membrane 5-Hydroxytryptamine2A (5-HT2A) Receptor in the Isolated Human Endothelium-Denuded Saphenous Vein via the Phosphatidylinositol 3-Kinase Pathway

“…We recently reported that in isolated human endothelium-denuded SVs, 5-HT 2A and 5-HT 1B receptors similarly contribute to 5-HT-induced vasoconstriction (24). The rings were treated with 300 μM L-NAME or L-NAME plus 100 nM wortmannin 15 min before the addition of 5-HT.…”