The effects of endothelin infusion on renal vascular resistance (RVR), glomerular filtration rate (GFR) and the interaction with locally generated endothelium-derived relaxant factor (EDRF) were studied in the rabbit isolated perfused kidney (IPK). For comparison the effects of infusions of angiotensin II (AII) and noradrenaline (NA) were also assessed. 2. Each kidney was perfused at a constant rate of 10 ml min-1 and alterations in RVR determined by measuring changes in perfusion pressure. GFR was determined by the clearance of [51Cr]-EDTA, using timed urine collections. 3. Endothelin (10(-11)-10(-9) M) produced a dose-related increase in RVR. Endothelin was approximately 30 times more potent in molar terms than AII and 500 times more than NA at inducing a 50 mmHg increase in perfusion pressure. 4. Endothelin appeared to be a weak inducer of EDRF release in the IPK as EDRF inhibitors methylene blue (10 microM) or haemoglobin (10 microM) only slightly augmented the increase in RVR at a given concentration of endothelin. In contrast the effect of NA on RVR was significantly increased by methylene blue (10 microM) whereas that induced by AII was not affected. 5. Endothelin infusion produced a significant, dose-dependent decrease in GFR of the IPK, contrasting with an increase in GFR during AII infusion and a minimal effect of NA on GFR. This supports evidence that AII is predominantly a constrictor of effernt glomerular arterioles and that NA constricts both afferent and efferent glomerular vessels. We suggest that the vasoconstrictive effect of endothelin in the kidney is predominantly preglomerular, which explains its effect on GFR.
摘要
在兔离体灌注肾（IPK）中研究了内皮素输注对肾血管阻力（RVR）、肾小球滤过率（GFR）的影响以及与局部产生的内皮源性舒张因子（EDRF）的相互作用。为作比较，还评估了血管紧张素 II（AII）和去甲肾上腺素（NA）输注的影响。2. 每个肾脏以 10 ml/min 的恒定速率灌注，通过测量灌注压力的变化来确定 RVR 的改变。GFR 通过定时收集尿液，测定[51Cr]-乙二胺四乙酸（EDTA）的清除率来确定。3. 内皮素（10^(-11) - 10^(-9) M）使 RVR 呈剂量相关增加。在内皮素诱导灌注压力升高 50 mmHg 时，按摩尔计算，其效力比 AII 约强 30 倍，比 NA 强 500 倍。4. 在内皮素诱导灌注压力升高 50 mmHg 时，按摩尔计算，其效力比 AII 约强 30 倍，比 NA 强 500 倍。4. 在内皮素诱导灌注压力升高 50 mmHg 时，按摩尔计算，其效力比 AII 约强 30 倍，比 NA 强 500 倍。4. 在内皮素诱导灌注压力升高 50 mmHg 时，按摩尔计算，其效力比 AII 约强 30 倍，比 NA 强 500 倍。5. 内皮素输注使 IPK 的 GFR 出现显著的剂量依赖性降低，这与 AII 输注期间 GFR 升高以及 NA 对 GFR 的影响最小形成对比。这支持了以下证据：AII 主要是出球小动脉的收缩剂，而 NA 使入球和出球小血管均收缩。我们认为内皮素在肾脏中的血管收缩作用主要在肾小球前，这解释了它对 GFR 的影响。
