Duke Lisa M, Eppel Gabriela A, Widdop Robert E, Evans Roger G
Department of Physiology, PO Box 13F, Monash University, Victoria 3800, Australia.
Hypertension. 2003 Aug;42(2):200-5. doi: 10.1161/01.HYP.0000083341.64034.00. Epub 2003 Jul 7.
The contributions of angiotensin II type 1 (AT1) and type 2 (AT2) receptors to the control of regional kidney blood flow were determined in pentobarbital-anesthetized rabbits. Intravenous candesartan (AT1 antagonist; 10 microg/kg plus 10 microg x kg(-1) x h(-1)) reduced mean arterial pressure (12%) and increased total renal blood flow (29%) and cortical laser-Doppler flux (18%) but not medullary laser-Doppler flux. Neither intravenous PD123319 (AT2 antagonist; 1 mg/kg plus 1 mg x kg(-1) x h(-1)) nor saline vehicle significantly affected these variables, and the responses to candesartan plus PD123319 were indistinguishable from those of candesartan alone. In vehicle-treated rabbits, renal-arterial infusions of angiotensin II (1 to 25 ng x kg(-1) x min(-1)) and angiotensin III (5 to 125 ng x kg(-1) x min(-1)) dose-dependently reduced renal blood flow (up to 51%) and cortical laser-Doppler flux (up to 50%) but did not significantly affect medullary laser-Doppler flux or arterial pressure. Angiotensin(1-7) (20 to 500 ng x kg(-1) x min(-1)) had similar effects but of lesser magnitude. CGP42112A (20 to 500 ng x kg(-1) x min(-1)) did not significantly affect these variables. After PD123319 administration, angiotensin II and angiotensin III dose-dependently increased medullary laser-Doppler flux (up to 84%), and reductions in renal blood flow in response to angiotensin II were enhanced. Candesartan abolished renal hemodynamic responses to the angiotensin peptides, even when given in combination with PD123319. We conclude that AT2 receptor activation counteracts AT1-mediated vasoconstriction in the renal cortex but also counteracts AT1-mediated vasodilatation in vascular elements controlling medullary perfusion. These mechanisms might have an important effect on the control of medullary perfusion under conditions of activation of the renin-angiotensin system.
在戊巴比妥麻醉的兔中确定了血管紧张素II 1型（AT1）和2型（AT2）受体对局部肾血流控制的作用。静脉注射坎地沙坦（AT1拮抗剂；10μg/kg加10μg·kg⁻¹·h⁻¹）可降低平均动脉压（12%），增加总肾血流量（29%）和皮质激光多普勒血流（18%），但不影响髓质激光多普勒血流。静脉注射PD123319（AT2拮抗剂；1mg/kg加1mg·kg⁻¹·h⁻¹）或生理盐水载体均未显著影响这些变量，且坎地沙坦加PD123319的反应与单独使用坎地沙坦的反应无明显差异。在给予载体的兔中，肾动脉输注血管紧张素II（1至25ng·kg⁻¹·min⁻¹）和血管紧张素III（5至125ng·kg⁻¹·min⁻¹）可剂量依赖性地降低肾血流量（高达51%）和皮质激光多普勒血流（高达50%），但对髓质激光多普勒血流或动脉压无显著影响。血管紧张素（1-7）（20至500ng·kg⁻¹·min⁻¹）有类似作用但程度较轻。CGP42112A（20至500ng·kg⁻¹·min⁻¹）未显著影响这些变量。给予PD123319后，血管紧张素II和血管紧张素III剂量依赖性地增加髓质激光多普勒血流（高达84%），且对血管紧张素II反应的肾血流量减少增强。坎地沙坦消除了对血管紧张素肽的肾血流动力学反应，即使与PD123319联合使用时也是如此。我们得出结论，AT2受体激活可抵消AT1介导的肾皮质血管收缩，但也可抵消AT1介导的控制髓质灌注的血管成分中的血管舒张。这些机制可能对肾素-血管紧张素系统激活条件下的髓质灌注控制有重要影响。
