| Research Abstract |
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.
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