Spitalewitz S, Chou S Y, Faubert P F, Porush J G
Circ Res. 1982 Dec;51(6):703-10. doi: 10.1161/01.res.51.6.703.
Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 +/- 1.0 (mean +/- SE) in six furosemide- and 11.3 +/- 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 +/- 2.6 and 26.7 +/- 2.7 ml/min per 100 g, respectively (P less than 0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 +/- 2.3 and 13.4 +/- 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolality and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 +/- 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.
尽管利尿剂的血流动力学效应已得到广泛研究,但其对肾髓质血流的影响仍不清楚。在本研究中,测定了麻醉状态下、禁水的犬以及在使用呋塞米(3mg/kg静脉注射,随后每小时2mg/kg静脉注射)、依他尼酸(3mg/kg静脉注射,随后每小时2mg/kg静脉注射)或氯噻嗪(10mg/kg静脉注射,随后每小时10mg/kg静脉注射)诱导的等容性利尿期间的肾血流动力学,包括通过白蛋白蓄积技术测量的乳头血浆流量,以及乳头组织溶质含量的相关变化。使用呋塞米和依他尼酸后肾血流量显著增加,而使用氯噻嗪后肾血流量显著减少。给予利尿剂60分钟后,6只接受呋塞米治疗的犬的乳头血浆流量为10.8±1.0(平均值±标准误),6只接受依他尼酸治疗的犬为11.3±2.6ml/min per 100g,均显著低于8只正常犬或8只接受氯噻嗪治疗的犬[分别为26.4±2.6和26.7±2.7ml/min per 100g(P<0.01)]。在5只接受呋塞米治疗和4只接受依他尼酸治疗的犬中,给予利尿剂10分钟后也观察到类似的低乳头血浆流量(分别为13.6±2.3和13.4±1.8ml/min per 100g)。在接受呋塞米和依他尼酸治疗的犬中,乳头渗透压和钠含量显著低于正常犬或接受氯噻嗪治疗的犬。在正常犬和接受氯噻嗪治疗的犬中,乳头钠含量相似,而后者的乳头渗透压显著降低。在测量乳头血浆流量时,四组犬的细胞外液体积相似;然而,接受呋塞米和依他尼酸治疗的犬的血浆肾素活性显著增加(P<0.01),而正常犬和接受氯噻嗪治疗的犬的血浆肾素活性保持不变。此外,在5只犬中,当使用沙拉新阻断血管紧张素II时输注呋塞米,其乳头血浆流量恢复正常(25.3±3.9ml/min per 100g),尽管其利尿和利钠情况与其他呋塞米组相似。这些数据表明,给予呋塞米、依他尼酸和氯噻嗪后,乳头血浆流量的调节独立于肾血流量,并提示血管紧张素II可能在接受呋塞米和依他尼酸治疗的犬的乳头血浆流量减少中起作用。