Long-term renal effects of unilateral ureteral obstruction and the role of endothelin
Long-term renal effects of unilateral ureteral obstruction and the role of endothelin
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DOI：
10.1046/j.1523-1755.2000.00159.x
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发表时间：
2000-07-01
影响因子：
19.6
通讯作者：
Davis, G
中科院分区：
文献类型：
--
作者：
Hammad, FT;Wheatley, AM;Davis, G
背景资料。血管紧张素II(Ang II)和内皮素(ET)参与了单侧输尿管梗阻(UUO)肾功能的改变。观察梗阻24小时后肾脏对血管紧张素Ⅱ的反应及波生坦对血管紧张素Ⅱ的阻断作用。用卡托普利阻断血管紧张素Ⅱ的内源性分泌后，在梗阻周给予波生坦治疗(n=10)和不加波生坦(n=8)的假手术(n=9)和UUO(N=10)后15~18天观察肾脏对AngⅡ的反应。另一组(N=9)在梗阻逆转后2个月进行类似的研究。在假手术组，Ang II使肾血排减少42+/-9%(P<；0.01)，肾小球滤过率减少30+/-8%(P<；0.01)，尿量减少44+/-9%(P<；0.001)，绝对排尿量减少52+/-9%(P<；0.001)，部分钠排泄量减少33+/-9%(P=0.054)。在先前梗阻的肾脏中，血管紧张素转换酶II不改变RBF，但使GFR增加10 6+/-40%(P<；0.01)，UV增加75+/-21%(P<；0.001)，UNaV增加190+/-60%(P<；0.001)，Fen增加40+/-13%(P<；0.05)。阻断组的波生坦治疗可阻止这些血管紧张素Ⅱ诱导的效应，并且对假手术的肾脏没有任何影响。梗阻逆转两个月后，肾脏的反应与对照肾相似。24小时UUO导致肾脏对血管紧张素转换酶II的反应出现暂时性异常，部分原因是梗阻时ET的作用。
Background. Angiotensin II (Ang II) and endothelin (ET) are involved in the alteration of renal function in unilateral ureteral obstruction (UUO). The renal response to Ang II following the reversal of a 24-hour UUO and the effect of ET blockade by bosentan during the time of obstruction were investigated.Methods. Following blockade of the endogenous production of Ang II by captopril, the renal response to Ang II was studied in rats 15 to 18 days after a 24-hour UUO (N = 10) or a sham operation (N = 9) both with (N = 10) and without (N = 8) bosentan treatment in the periobstruction period. Similar studies were performed in another group (N = 9) two months following the reversal of obstruction.Results. In the sham-operated group, Ang II reduced renal blood Row (RBF) by 42 +/- 9% (P < 0.01), glomerular filtration rate (GFR) by 30 +/- 8% (P < 0.01), urine volume (UV) by 44 +/- 9% (P < 0.001), and absolute (UNaV) and fractional sodium excretion (FENa) by 52 +/- 9% (P < 0.001) and 33 +/- 9% (P = 0.054), respectively. In the previously obstructed kidney, Ang II did not change RBF but increased GFR by 106 +/- 40% (P < 0.01), UV by 75 +/- 21% (P < 0.001), UNaV by 190 +/- 60% (P < 0.001), and FEN, by 40 +/- 13% (P < 0.05). Bosentan treatment in the obstructed group prevented these Ang II-induced effects and did not have any effect on the sham-operated kidney. Two months following reversal of the obstruction, the response of the kidney was similar to that of the control kidney.Conclusion. Twenty-four-hour UUO results in a temporary abnormality in the renal response to Ang II, which is due, in part, to the actions of ET at the time of obstruction.