Griffin K A, Picken M, Bidani A K
Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
Kidney Int. 1994 Oct;46(4):1010-8. doi: 10.1038/ki.1994.361.
The mechanisms by which antihypertensives exert a glomeruloprotective effect in the remnant kidney model remain controversial. Based on periodic tail-cuff BP measurements, the variable glomeruloprotective efficacy of antihypertensive agents has been ascribed to mechanisms other than or in addition to their ability to lower BP. To more precisely define the relationship between BP control and glomeruloprotection, systolic BP was continuously monitored radiotelemetrically at 10-minute intervals for approximately 65 days in rats after approximately 5/6 renal ablation. Rats with remnant kidneys received either no therapy or one of three antihypertensive regimens in their drinking water after the first week: enalapril, a triple therapy regimen (reserpine, hydralazine, hydrochlorothiazide); or a high dose triple therapy regimen. Although all antihypertensive regimens significantly lowered BP, considerable interanimal variability was observed. Additionally, marked lability of BP was present in both untreated and treated rats. Glomerular injury in individual animals (N = 34) was very strongly correlated with their overall averaged systolic BP during the final eight weeks (r = 0.91) and with the frequency of systolic BP readings > 150 mm Hg (r = 0.89). These data do not provide evidence of a therapeutic advantage for any of the regimens independent of their antihypertensive effects but indicate that the glomeruloprotective efficacy of these antihypertensive regimens is directly proportional to their antihypertensive efficiency.
在残余肾模型中,抗高血压药物发挥肾小球保护作用的机制仍存在争议。基于定期的尾套血压测量,抗高血压药物不同的肾小球保护效果被归因于其降低血压能力之外或之外兼有的其他机制。为了更精确地界定血压控制与肾小球保护之间的关系,在约5/6肾切除术后的大鼠中,通过无线电遥测以10分钟的间隔连续监测收缩压约65天。残余肾大鼠在第一周后,要么不接受治疗,要么在饮水中接受三种抗高血压方案之一:依那普利、三联疗法方案(利血平、肼屈嗪、氢氯噻嗪);或高剂量三联疗法方案。尽管所有抗高血压方案均显著降低了血压,但观察到动物间存在相当大的变异性。此外,未治疗和治疗的大鼠均存在明显的血压波动。个体动物(N = 34)的肾小球损伤与它们在最后八周的总体平均收缩压(r = 0.91)以及收缩压读数>150 mmHg的频率(r = 0.89)密切相关。这些数据并未提供任何一种方案独立于其抗高血压作用之外的治疗优势的证据,但表明这些抗高血压方案的肾小球保护效果与其抗高血压效率直接成正比。