大鼠肾小球免疫损伤：血管紧张素II和α-肾上腺素能抑制剂的影响

Glomerular immune injury in the rat: the influence of angiotensin II and alpha-adrenergic inhibitors.

作者信息

Blantz R C, Tucker B J, Gushwa L C, Peterson O W, Wilson C B

出版信息

Kidney Int. 1981 Oct;20(4):452-61. doi: 10.1038/ki.1981.161.

DOI:10.1038/ki.1981.161

Abstract

Nephron filtration rate (SNGFR) decreases significantly after the administration of large doses of antiglomerular basement membrane antibody (anti-GBM) as a result of reductions in both nephron (renal) plasma flow (RPF) and the glomerular permeability coefficient (LpA). We have examined the participation of angiotensin II (AII) and alpha-adrenergic activity in this process in paired studies in three groups of Munich-Wistar rats: group 1, control and untreated; group 2, rats receiving continuous infusion of sar1-ala8-AII (1 microgram . kg of body wt-1 . min-1), and AII receptor antagonist; and group 3, rats receiving continuous infusion of phentolamine (27 micrograms . kg body wt-1 . min-1), a dose sufficient to block alpha-adrenergic responses. In group 1, SNGFR decreased from 58 +/- 4 to 35 +/- 6 nl . min-1 . g kidney wt-1 (P less than 0.001) after anti-GMB administration due to reductions in RPF (272 +/- 35 to 170 +/- 52 nl . min-1 . g of kidney wt-1, P less than 0.0001) and LpA (0.13 +/- 0.03 to 0.04 +/- 0.01 nl . sec-1 . g of kidney wt-1 . mm Hg-1, P less than 0.02). In group 2, the sar1-ala8-AII-infused rats. SNGFR decreased to a greater extent than it did in group 1 (P less than 0.01) (55 +/- 2 to 18 +/- 6 nl . min-1 . g of kidney wt-1, P less than 0.005) due to a greater reduction in RPF and a similar decrease in LpA. In group 3, phentolamine infusion prevented the decrease in SNGFR (52 +/- 3 to 52 +/- 4 nl . min-1 . g of kidney wt-1, NS) due primarily to elimination of vasoconstriction and a significantly lesser reduction in LpA (0.10 +/- 0.02 to 0.07 +/- 0.01 nl . sec-1 . g of kidney wt-1 . mm HG-1). There were no morphologic differences after anti-GBM administration that were unique to group 3. Blockade of AII activity does not prevent immune induced vasoconstriction or the reduction in LpA. alpha-Adrenergic blockage (1) prevents acute immune induced vasoconstriction and (2) partially prevents the imune induced reduction in LpA.

摘要

给予大剂量抗肾小球基底膜抗体（anti - GBM）后，肾单位滤过率（SNGFR）显著降低，这是由于肾单位（肾）血浆流量（RPF）和肾小球通透系数（LpA）均降低所致。我们在三组慕尼黑 - 威斯塔大鼠的配对研究中，研究了血管紧张素II（AII）和α - 肾上腺素能活性在此过程中的作用：第1组，对照且未治疗；第2组，持续输注sar1 - ala8 - AII（1微克·千克体重-1·分钟-1）的大鼠，以及AII受体拮抗剂；第3组，持续输注酚妥拉明（27微克·千克体重-1·分钟-1）的大鼠，该剂量足以阻断α - 肾上腺素能反应。在第1组中，给予抗GBM后，SNGFR从58±4降至35±6纳升·分钟-1·克肾重-1（P＜0.001），原因是RPF降低（从272±35降至170±52纳升·分钟-1·克肾重-1，P＜0.0001）和LpA降低（从0.13±0.03降至0.04±0.01纳升·秒-1·克肾重-1·毫米汞柱-1，P＜0.02）。在第2组中，输注sar1 - ala8 - AII的大鼠，SNGFR降低的程度比第1组更大（P＜0.01）（从55±2降至18±6纳升·分钟-1·克肾重-1，P＜0.005），这是由于RPF降低幅度更大且LpA有类似程度的降低。在第3组中，输注酚妥拉明可防止SNGFR降低（从52±3降至52±4纳升·分钟-1·克肾重-1，无显著性差异），主要是因为消除了血管收缩，且LpA降低幅度明显较小（从0.10±0.02降至0.07±0.01纳升·秒-1·克肾重-1·毫米汞柱-1）。给予抗GBM后，第3组没有独特的形态学差异。阻断AII活性并不能防止免疫诱导的血管收缩或LpA降低。α - 肾上腺素能阻断（1）可防止急性免疫诱导的血管收缩，（2）部分防止免疫诱导的LpA降低。