The role of endothelium-derived hyperpolizing factor in shear stress in coronary resistance vessels

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13670764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hyogo College of Medicine
• Principal Investigator: OHYANAGI Mitsumasa Hyogo College of Medicine, Associate professor, 医学部, 助教授 (90131573)
• Project Period (FY): 2001 – 2002
• Keywords: endothelium-derived hyperpolarizing factor / coronary arteriole / Flow-induced dilation / heset failure / microcirculation

Research Abstract

Study 1. The mechanism of flow-dependent vasodilation of human small coronay arteries.
Human coronary arterioles were dissected and cannulated. At variable flow, changes in their internal diameter were examined with videomicroscopy. We then tested the response to flow with and without inhibition of NO syntheses, NG-Monomethy-L-atginine (L-NMMA). Flow-dependent vasodilation was significantly attenuated by inhibition of NO syntheses, and vasodilation was partially attenuated with inhibition of Gi and KATP channels. Endothelial-derived NO-dependent mechanisms play an important role in flow-dependent vasodilation in human coronaty microvessels. Moreover, endothelium-derived hyperpolarizing factor (EDHF) was involved in FTD that was not blocked completely by L-NMMA and INDO. FID was significantly decreased by charybdotoxin plus apamin or tetrabutylamnmonium. Therefore, EDHF-mediated dilation of human coronary arterioles is mediated by K^+ channels including Kca channels.
Study 2. Enhanced rel ease of endothelium-derived hyperpolarizing factor in small coronary arteries from rats with congestive heart failure (CHF).
The aim of this study was to determine whether flow-induced dilation (FID) is altered in small coronary arteries from CHF rats and to characterize the role of EDHF in this process. The small coronary arteries were isolated from control rats and from rats with CHF induced by left coronary artery ligation and were cannulated with flow. There was no significant difference in FED between the two groups. FID in control rat vessels showed greater attenuated by L-NMMA than vessels from CHF rats. Pretreatment with indomethacin (INDO) only minimally affected FID. FID was attenuated to a greater degree in CHF rat vessels by KCl in the presence of L-NMMA and INDO compared to control rat. FID was abolished by removal of the endothelium. FID was significantly decreased in vessels from CHF rats in response to charybdotoxin plus apamin or tetrabutylamnmomium when compared to control rat vessels, while 17-octadecynoic acid had only minimal affect on FID in both control and CHF rat vessels FID of small coronary arteries is mediated by K^+ channels, including Kca channels. EDHF-mediated dilation may compensate for the loss of NO-mediated dilation in CHF.