Uchida T, Hayashi K, Kido H, Watanabe M
Central Research Laboratory, Green Cross Corporation, Osaka, Japan.
J Pharm Pharmacol. 1992 Jan;44(1):39-43. doi: 10.1111/j.2042-7158.1992.tb14360.x.
The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
在麻醉犬中研究了托拉塞米(0.1和1毫克/千克,静脉注射)和呋塞米(3毫克/千克)在存在血管紧张素II和内皮素-1的情况下对肾血流动力学和排泄反应的影响。在整个实验过程中,将血管紧张素II或内皮素-1持续输注到肾动脉中,并将一剂托拉塞米或呋塞米注入臂静脉。以5纳克/千克·分钟-1的剂量持续肾内动脉(i.r.a.)输注血管紧张素II,可增加肾血管阻力(RVR),降低肾血流量(RBF)和肾小球滤过率(GFR),但对全身平均动脉压(MAP)无影响。在输注血管紧张素II期间,尿钠排泄量(UNaV)和尿流量(UF)显著降低。在存在血管紧张素II的情况下静脉注射托拉塞米导致UF、UNaV和尿钾排泄量(UKV)呈剂量依赖性增加,而RVR降低伴随着RBF增加。尽管两组的利水和利钠程度相同,但呋塞米组的UKV高于托拉塞米组。以1.5纳克/千克·分钟-1的剂量持续i.r.a.输注内皮素-1对肾血流动力学产生的影响与血管紧张素II相似;然而,与血管紧张素II产生的影响相比,其起效极其缓慢。尽管肾血流动力学相对较早出现抑制,但内皮素-1仅在后期导致UF、UNaV和UKV显著降低。在该模型中,托拉塞米和呋塞米也产生了充分的利尿作用。(摘要截断于250字)