Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II
Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II
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DOI：
10.1113/eph8602219
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发表时间：
2001-09-01
影响因子：
2.7
通讯作者：
Sadowski, J
中科院分区：
文献类型：
--
作者：
Dobrowolski, L;Badzynska, B;Sadowski, J
我们最近发现，速尿(速尿)后的钠尿与骨髓循环的严重抑制有关。在本研究中，在给药之前，通过向动物体内注入5%的生理盐水来改变氯化钠的小管转运，以阐明药物的小管和血管效应之间的可能的相互关系。此外，用血管紧张素转换酶抑制剂卡托普利(1 mg kg(-1)，iv)或血管紧张素AT(I)受体选择性抑制剂氯沙坦(10 mg kg(-1)，iv)药理阻断肾素-血管紧张素系统。用激光多普勒血流仪测定静脉注射速尿(0.25 mg·kg~(-1))1h后对大鼠肾脏髓质和皮质循环及肾脏钠、水和总溶质排泄量的影响。在无治疗前，速尿对髓质血流量的减少(36.6%+/-6.0%)明显大于皮质血流量(10.1%+/-1.0%；P<；0.001)。高渗盐水负荷后UNaV高的大鼠(非负荷大鼠的UNaV为2.0+/-0.4vs.0.4+/-0.1mU·moL·min(-1))，髓质与皮质的差异无统计学意义：分别为21.1+/-3.9%和15.8+/-1.5%。在非常高的UNaV(9.5+/-1.1 mU·mol·min(-1))条件下，速尿治疗后延髓(7.6+/-7.7%)比皮质(16.2+/-2.6%)的血流下降更小。卡托普利(22.0+/-3.3%)和氯沙坦(2.8+/-11.8%)可使骨髓血流量下降减轻。高渗盐水或血管紧张素II阻滞剂不能改变皮质血流量的减少。先前的盐负荷取消了速尿后对髓质血流的抑制，证实了肾小管运输状态和血管收缩之间的联系。通过阻断肾素-血管紧张素系统对反应的类似修饰表明，该系统参与了髓质血管收缩的机制。
We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg kg(-1), i.v.), or losartan, a selective inhibitor of angiotensin AT(I) receptor (10 mg kg(-1), i.v.). The effects of frusemide (0.25 mg kg(-1) i.v., then the same dose given over 1 h) on renal medullary and cortical circulation (using laser-Doppler flowmetry) and renal excretion of sodium (UNaV), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/- 1.0 %; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high UNaV after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0.1 mu mol min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, respectively. At very high UNaV (9.5 +/- 1.1 mu mol min(-1)) the post-frusemide decrease in blood flow tended to he smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.