Wilkes B M, Bellucci A
J Lab Clin Med. 1983 Dec;102(6):909-17.
Angiotensin (AII) binds to specific glomerular receptors to modulate glomerular filtration rate (GFR) in the normal kidney. To test the hypothesis that altered AII binding to the glomerulus may contribute to the decreased GFR in acute renal failure (ARF) we studied the properties of glomerular AII receptors in models of ARF. ARF was induced in rats by either mercuric chloride (2.0 or 4.5 mg/kg) or 60 min renal ischemia. Outer cortical glomeruli isolated by sieving techniques were studied by equilibrium binding analysis. Scatchard analysis revealed one class of high-affinity receptors over a wide range of concentrations (10(-11)M to 10(-8)M). Angiotensin binding to specific glomerular receptors was studied at 2 and 24 hr after high-dose mercuric chloride. Glomerular AII receptor density was unchanged after mercuric chloride ARF [2 hr: 783 +/- 96 (N = 6), 24 hr: 765 +/- 69 (N = 4); normal control: 718 +/- 64 (N = 9)]. Likewise, the equilibrium affinity constant was unaltered after HgCl2 [2 hr: 1.85 +/- 0.28 X 10(8)M-1 (N = 6); 24 hr: 1.80 +/- 0.25 X 10(8)M-1 (N = 4); normal control: 2.02 +/- 0.21 X 10(8)M-1 N = 9)]. Plasma angiotensin II levels were elevated 2 hr after HgCl2 (normal 16.2 +/- 2.3 pg/ml; 2 hr 47.6 +/- 4.8) and returned to normal by 24 hr (17.2 +/- 2.4 pg/ml). Additional experiments performed 2 weeks after low-dose HgCl2-induced ARF and at 24 hr after unilateral renal artery clamp also demonstrated normal AII receptor affinity and density. These studies demonstrated that glomerular AII receptor binding is unaltered during the initiation, maintenance, and recovery phases of ARF. Changes in the binding characteristics of glomerular AII receptors do not play a role in the pathogenesis of ARF.
血管紧张素(AII)与特定的肾小球受体结合,以调节正常肾脏的肾小球滤过率(GFR)。为了验证肾小球AII结合改变可能导致急性肾衰竭(ARF)时GFR降低这一假说,我们研究了ARF模型中肾小球AII受体的特性。通过氯化汞(2.0或4.5mg/kg)或60分钟肾缺血诱导大鼠发生ARF。采用平衡结合分析法研究通过筛分技术分离的外皮质肾小球。Scatchard分析显示在较宽浓度范围(10⁻¹¹M至10⁻⁸M)内存在一类高亲和力受体。在高剂量氯化汞处理后2小时和24小时研究血管紧张素与特定肾小球受体的结合。氯化汞诱导的ARF后肾小球AII受体密度未改变[2小时:783±96(N = 6),24小时:765±69(N = 4);正常对照:718±64(N = 9)]。同样,氯化汞处理后平衡亲和常数也未改变[2小时:1.85±0.28×10⁸M⁻¹(N = 6);24小时:1.80±0.25×10⁸M⁻¹(N = 4);正常对照:2.02±0.21×10⁸M⁻¹ N = 9)]。氯化汞处理后2小时血浆血管紧张素II水平升高(正常16.2±2.3pg/ml;2小时47.6±4.8),并在24小时恢复正常(17.2±2.4pg/ml)。在低剂量氯化汞诱导的ARF后2周以及单侧肾动脉夹闭后24小时进行的额外实验也显示AII受体亲和力和密度正常。这些研究表明,在ARF的起始、维持和恢复阶段,肾小球AII受体结合未改变。肾小球AII受体结合特性的变化在ARF的发病机制中不起作用。