Lai En Yin, Persson A Erik G, Bodin Birgitta, Källskog Orjan, Andersson Arne, Pettersson Ulrika, Hansell Peter, Jansson Leif
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1616-23. doi: 10.1152/ajpendo.00640.2006. Epub 2007 Feb 6.
Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate whether exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo, we found that ET-1 (5 nmol/kg) consistently and markedly decreased total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin A (ET(A)) receptor (BQ-123) nor endothelin-B (ET(B)) receptor (BQ-788) antagonists, alone or in combination, could prevent this reduction in blood flow. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation, we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ET(A) receptors.
内皮素 -1（ET -1）是一种强效的内皮源性血管收缩剂，它还能刺激胰岛素释放。本研究的目的是评估外源性给予的ET -1是否会影响大鼠体内胰腺胰岛的血流以及小鼠体外胰岛小动脉的反应性。此外，我们旨在确定参与此类反应的ET受体亚型。当应用微球技术测量体内胰岛血流灌注时，我们发现ET -1（5 nmol/kg）持续且显著地降低了胰腺总体血流，尤其是胰岛血流，尽管对血压影响较小。内皮素A（ET(A)）受体拮抗剂（BQ -123）和内皮素B（ET(B)）受体拮抗剂（BQ -788）单独或联合使用均不能阻止这种血流减少。为避免体内的混杂相互作用，我们还研究了分离的灌注小鼠胰岛中小动脉的血管反应性。在后者的制备中，我们证明了对ET -1的剂量依赖性收缩反应。给予BQ -123可阻止这种反应，而BQ -788则使反应向右移位。总之，胰腺胰岛血管系统对外源性ET -1高度敏感，ET -1主要通过ET(A)受体介导其作用。
