Effects of antihypertensive drugs on glomerular morphology.
Effects of antihypertensive drugs on glomerular morphology.
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抗高血压药物对肾小球形态的影响。
DOI：
10.1038/ki.1989.239
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发表时间：
1989
影响因子：
19.6
通讯作者：
Ichikawa,I
中科院分区：
文献类型：
--
作者：
Yoshida,Y;Kawamura,T;Ikoma,M;Fogo,A;Ichikawa,I
抗高血压药物对肾小球形态的影响。我们对肾大部切除术 (sNPX) 后具有高度异质性肾小球病变的残肾获得的连续切片进行三维组织学分析，同时对单个肾小球的肾小球大小和硬化程度进行定量。 sNPX 后 4 至 6 周（第 I 组，N = 7），90% 的肾小球出现轻度硬化（硬化指数，SI；0 至 4 级< 1.5），肾小球最大平面面积 (PAmax) 与 SI 之间呈强正相关。 sNPX 后 12 周（II 组，N = 6），超过 50% 的肾小球出现晚期硬化（平均 SI：1.88），并且在轻度至中度硬化的肾小球中 PAmax 和 SI 之间再次发现显着正相关（SI = 1.5），而在晚期硬化的肾小球中，这两个变量呈负相关。给予依那普利（50毫克/升饮用水）或肼屈嗪（200毫克/升）+利血平（10毫克/升）+氢氯噻嗪（50毫克/升）12周（第III组，TV = 12）可显着减轻硬化至可比较的程度（平均SI：0.15 vs. 0.22）。前者的抗高血压治疗使肾小球毛细血管压(PGc)降低至正常范围，而后者的三联药物治疗对PGC基本没有影响。值得注意的是，SI 和 PAmax 之间的正相关性并未受到这些抗高血压药物的影响。两个治疗组的肾小球 SI 均表示为 PAmax 的一阶函数。相关系数与未治疗的 II 组残余肾小球中发现的相同，因此无论药物治疗如何，硬化程度在数学上与肾小球大小唯一相关。因此，在给定的残肾内，肾小球肥大的程度与硬化程度直接相关，而改变的肾小球血流动力学模式在确定肥大的程度方面几乎没有调节作用。依那普利和三联药物治疗在全身血压方面的降压剂量相同，在保护肾小球结构方面具有相同的效力。这种抗硬化效力的主要决定因素似乎与药物抑制肾小球生长的效力有关，而不是与对肾小球中出现的异常血流动力学的影响有关。
Effects of antihypertensive drugs on glomerular morphology. We quantitated the glomerular size and the degree of sclerosis simultaneously in individual glomeruli with the use of three-dimensional histological analysis on serial sections obtained from remnant kidneys with highly heterogeneous glomerular lesions after subtotal nephrectomy (sNPX). Four to six weeks after sNPX (Group I, N = 7), 90% of glomeruli had mild sclerosis (sclerosis index, SI; < 1.5 on a 0 to 4 scale) with a strong positive correlation between the maximum planar area of glomerulus (PAmax) versus SI. Twelve weeks after sNPX (Group II, N =6) more than 50% of glomeruli had advanced sclerosis (average SI: 1.88), and a significant positive correlation was again found between PAmax and SI in glomeruli with mild to modest sclerosis (SI = 1.5), whereas these two variables were correlated inversely in glomeruli with advanced sclerosis. Administration of enalapril (50 mg/liter drinking water) or hydralazine (200 mg/liter) + reserpine (10 mg/liter) + hydrochlorothiazide (50 mg/liter) for 12 weeks (Group III, TV = 12) markedly attenuated the sclerosis to comparable degrees (average SI: 0.15 vs. 0.22). The former antihypertensive therapy decreased glomerular capillary hydraulic pressure (PGc)t0 normal range, whereas the latter triple drug therapy was largely without efifect on PGC. Of note, the positive correlation between SI and PAmax remained unaffected by these anti-hypertensive drugs. SI of the glomeruli from both treated groups was expressed as a first-order function of PAmax. The correlation coefficient is identical to that found in non-treated Group II remnant glomeruli, so that the degree of sclerosis is mathematically uniquely correlated with the glomerular size, regardless of drug treatment. Thus, within a given remnant kidney, the magnitude of glomerular hypertrophy has a direct correlation with the degree of sclerosis, while the altered glomerular hemodynamic pattern has little modulatory role in determining the magnitude of this hypertrophy. Enalapril and triple drug therapy, at equi-depressor doses in regard to systemic blood pressure, had identical potency in sparing glomerular structure. The primary determinant for this antisclerotic potency appears to be related to the drugs' potency to inhibit glomerular growth rather than an effect on the abnormal hemodynamics which develop in the glomerulus.