Furosemide increases urine 6-keto-prostaglandin F1 alpha. Relation to natriuresis, vasodilation, and renin release.
Furosemide increases urine 6-keto-prostaglandin F1 alpha. Relation to natriuresis, vasodilation, and renin release.
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呋塞米会增加尿液中 6-酮前列腺素 F1 α 的含量。
DOI：
10.1161/01.hyp.4.5.634
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Halushka,PV
中科院分区：
文献类型：
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作者：
Wilson,TW;Loadholt,CB;Privitera,PJ;Halushka,PV
虽然之前的研究表明前列腺素 (PG) 介导呋塞米的肾血管舒张和肾素释放作用，但剂量反应关系尚未明确，也没有涉及具体的 PG。前列环素 (PGIj) 在肾皮质中合成，是一种血管扩张剂，可以释放肾素，因此可以介导呋塞米的这些作用。作者测量了麻醉犬静脉推注呋塞米剂量增加后 PGI2 水解产物 6-酮前列腺素 Fla (U6kV) 的尿排泄量。与对照狗相比，呋塞米 0.1 mg/kg 增加了尿量 (V) 和钠排泄 (UNaV)，但没有改变 U6kV、p-氨基马尿酸清除率 (CPAH) 或血浆肾素活性 (PRA)。较高剂量（1.0 mg/kg）增加了 V、UNaV、U6kV（23.4±11.0 至 56.5±18.7 ng/15 分钟，p< 0.05）、CPAH（121±40 至 304±80 ml/min，p< 0.05）和 PRA（5.4±2.2 至 11.7±4.4，p< 0.05） 0.05）。 U6kV 与 V 或 UNaV 之间不存在相关性，但 U6kV 与 CPAH 之间存在相关性（r= 0.81，p < 0.001），并且在每次剂量呋塞米后 U6k V 增加百分比与 PRA 增加百分比之间存在相关性（r= 0.59，p < 0.05）。在单独的实验中，我们通过将 PG 独立的血管舒张促胰液素注入肾动脉来评估增加肾血流量 (RBF) 对 U6kV 的影响。单肾RBF从124±32增加到202±21 ml/min（p<0.01），CPAH从56±18增加到83±42 ml/min（p<0.05），但U6kV没有变化。吲哚美辛降低 U6kV，但不影响促胰液素诱导的 RBF 或 CPAH 增加。结果表明，低剂量速尿会引起尿钠排泄，且对 U6kV 没有影响。相反，呋塞米诱导的血管舒张和肾素释放需要更高的剂量，并且与 U6kV 增加相关。由于促胰液素可以在不改变 U6kV 的情况下增加 RBF，因此我们认为速尿引起的 U6kV 增加并不是继发于 RBF 增加的。相反，呋塞米似乎会释放肾脏 PGI2，其部分介导血管舒张和肾素释放，并以 6-酮前列腺素 Fla 的形式在尿液中排泄。（Hypertension 4: 634-641, 1982）
While previous studies have shown that prostaglandins (PG) mediate the renal vasodilating and renin-releasing actions of furosemide, the dose-response relationship has not been defined nor has the specific PG involved. Prostacyclin (PGIj) is synthesized in the renal cortex, is a vasodilator, can release renin and, therefore, could mediate these actions of furosemide. The authors measured urinary excretion of the PGI2 hydrolysis product 6-keto prostaglandin Fla (U6kV) in response to increasing intravenous bolus doses of furosemide in anesthetized dogs. Furosemide 0.1 mg/kg increased urine volume (V) and sodium excretion (UNaV) compared to control dogs, but did not change U6kV, p-aminohippurate clearance (CPAH), or plasma renin activity (PRA). A higher dose (1.0 mg/kg) increased V, UNaV, U6kV (23.4±11.0 to 56.5±18.7 ng/15 min, p< 0.05), CPAH (121±40 to 304±80 ml/min, p< 0.05), and PRA (5.4±2.2 to 11.7±4.4, p< 0.05). There was no correlation between U6kV and V or UNaV, but correlations existed between U6kV and CPAH (r= 0.81, p< 0.001) and between the percent increase of U6k V and the percent increase of PRA fol lowing each dose of furosemide (r= 0.59, p< 0.05). In separate experiments, we assessed the effects of increasing renal blood flow (RBF) on U6kV, by infusing the PG-independent vasodilator secretin into a renal artery. RBF of the single kidney increased from 124±32 to 202±21 ml/min (p< 0.01) and CPAH from 56±18 to 83±42 ml/min (p< 0.05), but U6kV did not change. Indomethacin reduced U6kV but did not affect secretin-induced increases in RBF or CPAH. The results indicate that furosemideinduced natriuresis occurs at low doses and in the absence of an effect on U6kV. In contrast, furosemide induced vasodilation and renin release required higher doses and were associated with increased U6kV. Because secretin can increase RBF without changing U6kV, we suggest that furosemide-induced increases in U6kV are not secondary to increased RBF. Rather, it appears that furosemide releases renal PGI2 which, in part, mediates vasodilation and renin release, and was excreted in urine as 6-keto-prostaglandin Fla.(Hypertension 4: 634-641, 1982)