[Pharmacological studies on responsiveness of 5-hydroxytryptamine in overcoming perioperative spasm of coronary artery bypass graft].
In ischemic heart diseases, the use of the internal thoracic artery (ITA) as an arterial graft has been associated with longer survival and better quality of life. However, it has been reported that vasospasm of the ITA graft frequently occurs and increases perioperative and postoperative morbidity. Serotonin (5-HT) plays an important role in the occurrence of vasospasm. We examined 5-HT receptor subtypes responsible for the 5-HT-induced vasocontraction in the human ITA. The contractile response caused by 5-HT was mediated by activation of not only 5-HT(2A) receptors but also 5-HT(1B) receptors. We also examined the relationship between 5-HT-induced vasocontraction of the rabbit femoral artery and arteriosclerosis using the arteriosclerosis model of repeated balloon-injury. The contractile response caused by 5-HT in the femoral artery with arteriosclerosis was significantly greater than that in the normal artery. Additionally, we demonstrated that insulin induced internalization of 5-HT(2A) receptors from the plasma membrane in HEK293 cells. Diabetes mellitus (DM) is a risk factor for ischemic heart diseases. We evaluated the 5-HT-induced vasocontraction, mediated by activation of 5-HT(2A) and 5-HT(1B) receptors, in the ITA obtained from patients with DM or without DM undergoing coronary bypass surgery. The contractile response caused by 5-HT in the ITA from patients with DM was significantly greater than that from patients without DM. Our findings suggest that when the ITA is used as an arterial graft, simultaneous treatment with 5-HT(2A) and 5-HT(1B) receptor antagonists is useful to prevent 5-HT-induced vasospasm, especially in patients with DM.
Tanaka
Naoko
N
First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Miyazaki, Japan. naokot@phoenix.ac.jp
D000818:Animals; D001026:Coronary Artery Bypass; D003329:Coronary Vasospasm / Q000209:etiology* / Q000517:prevention & control*; D048909:Diabetes Complications; D015195:Drug Design; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D008323:Mammary Arteries / Q000637:transplantation; D011183:Postoperative Complications / Q000209:etiology* / Q000517:prevention & control*; D011817:Rabbits; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D014654:Vascular Patency
D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin