Gerber J G, Nies A S
Kidney Int. 1980 Oct;18(4):454-9. doi: 10.1038/ki.1980.158.
The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects of furosemide because these maneuvers have been reported to blunt the tubuloglomerular feedback in micropuncture studies. In addition, we also used two structurally different nonsteroidal antiinflammatory drugs to assess the importance of prostaglandins to achieve furosemide's renal vasodilatation. Furosemide (5 mg/kg, i.v.) increased renal blood flow in volume-depleted animals from a baseline flow of 141 +/- 28 ml/min to a maximum of 176 +/- 35 ml/min at 6 min after furosemide administration. If the animals were pretreated with a high-salt diet and i.m. DOCA for 5 days, furosemide administration produced no renal vascular effects but still caused a large diuresis, and these dogs still had a responsive renal vascular bed to infused prostaglandin E2. In addition, kidneys rendered non-filtering in volume-depleted animals had no renal vascular response to furosemide. Volume-depleted animals, pretreated with either indomethacin or sodium meclofenamate, did not have a renal vascular response to furosemide although they did have a diuretic response and a responsive renal vasculature to prostaglandin E2. From our data, we hypothesize that the renal vascular response to furosemide is secondary to a tubular mechanism mediated by a vasodilatory prostaglandin. Because furosemide has been shown to disrupt the tubuloglomerular feedback mechanism, and the two maneuvers, DOCA plus salt treatment and lack of filtration, blunt the tubuloglomerular feedback response as well as inhibit the renal vascular response to furosemide, we further hypothesize that furosemide-induced renal vasodilation may be secondary to the disruption of an active tubuloglomerular feedback mechanism.
在杂种犬中研究了呋塞米增加肾血流量的情况，因为这可能与肾小管-肾小球反馈机制有关。在犬中采用了两种方法，即脱氧皮质酮（DOCA）加食盐处理和抑制肾小管液流，以评估呋塞米对肾血管的影响，因为在微穿刺研究中已报道这些方法可减弱肾小管-肾小球反馈。此外，我们还使用了两种结构不同的非甾体抗炎药来评估前列腺素对实现呋塞米肾血管舒张作用的重要性。呋塞米（5mg/kg，静脉注射）使容量减少的动物的肾血流量从基线流量141±28ml/min增加到给药后6分钟时的最大值176±35ml/min。如果动物预先接受高盐饮食和肌肉注射DOCA 5天，给予呋塞米不会产生肾血管效应，但仍会引起大量利尿，并且这些犬对注入的前列腺素E2仍有反应性肾血管床。此外，在容量减少的动物中使肾脏失去滤过功能后，对呋塞米没有肾血管反应。容量减少的动物，预先用吲哚美辛或甲氯芬那酸钠处理，对呋塞米没有肾血管反应，尽管它们有利尿反应并且对前列腺素E2有反应性肾血管系统。根据我们的数据，我们假设对呋塞米的肾血管反应继发于由血管舒张性前列腺素介导的肾小管机制。因为呋塞米已被证明会破坏肾小管-肾小球反馈机制，并且DOCA加食盐处理和缺乏滤过这两种方法会减弱肾小管-肾小球反馈反应以及抑制对呋塞米的肾血管反应，我们进一步假设呋塞米诱导的肾血管舒张可能继发于活跃的肾小管-肾小球反馈机制的破坏。
