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The Control of Glomerular hemodynamics and its significance in renal dysfunction and hypertension

肾小球血流动力学的控制及其在肾功能不全和高血压中的意义

基本信息

批准号：
10470215
负责人：
ITO Sadayoshi
金额：
$ 8.19万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Using isolated microperfused glomerular afferent arterioles, we investigated the mechanism that controls glomerular hemodynamics and their significance in progressive renal dysfunction and hypertension. We first examined interactions among angiotensin type 1 and type 2 (ATィイD21ィエD2 and ATィイD22ィエD2) receptors, nitric oxide (NO), 20-HETE and EET, major metabolites of arachidonic acid via cytochrome P450 pathways in rabbit afferent arterioles. We found that 1) both NO and EET are vasodilators which atlenuate ATィイD21ィエD2 receptor-mediated vasoconstriction, 2) activation of ATィイD22ィエD2 receptor causes vasodilation, 3) the mechanism of ATィイD22ィエD2 receptor-mediated vasodilation involves EET, but no NO, 4) 20-HETE is important for Ang II-induced vasoconstriction.We then examined the role of ATィイD22ィエD2 in the vascular reactivity of the afferent arteriole obtained from prehypertensive young (4 weeks old) spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto rats (WKY). Ang II-induced vasoconstriction was stronger in SHR than WKY afferent arterioles. ATィイD22ィエD2 receptor antagonism augmented Ang II-induced vasoconstriction only WKY afferent arterioles, resulting in no difference in Ang II action between the two. In the presence of an ATィイD21ィエD2 receptor antagonist, Ang II caused vasodilation in preconstricted afferent arteriole of WKY. This dilation was blocked by pretreatment with an ATィイD22ィエD2 receptor antagonist. On the other hand, such dilation was not observed in Ang II-induced afferent arteriolar constriction is exaggerated due, at least in part, to impained function of the ATィイD22ィエD2 receptor-mediated vasoditor mechanism.

利用离体微灌注的肾小球传入小动脉，我们研究了控制肾小球血流动力学的机制及其在进行性肾功能不全和高血压中的意义。我们首先研究了血管紧张素1型和2型（AT β D21 β D2和AT β D22 β D2）受体，一氧化氮（NO），20-HETE和EET之间的相互作用，花生四烯酸的主要代谢产物通过细胞色素P450途径在兔传入小动脉。我们发现：1）NO和EET都是舒张血管的物质，可减弱AT β D21受体介导的血管收缩，2）AT β D22受体的激活可引起血管舒张，3）AT β D22受体介导的血管舒张作用的机制与EET有关，而与NO无关，4）20-HETE在Ang Ⅱ引起的血管收缩中起重要作用，我们研究了AT受体D22-HETE D2在高血压前期青年人传入小动脉血管反应性中的作用。（4周龄）自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto大鼠（WKY）。Ang Ⅱ诱导的SHR血管收缩作用强于WKY传入小动脉。AT β D22受体拮抗剂仅增强WKY传入小动脉的Ang II诱导的血管收缩，导致两者之间的Ang II作用无差异。在AT受体D21受体拮抗剂存在下，Ang Ⅱ引起WKY预收缩的传入小动脉血管舒张。这种扩张被阻断预处理与AT β D22受体拮抗剂。另一方面，在Ang II诱导的传入小动脉收缩中没有观察到这种扩张，这至少部分是由于AT β D22受体介导的血管舒张机制的功能受损而被夸大。