Stier C T, Roberts L J, Wong P Y
Department of Pharmacology, New York Medical College, Valhalla.
J Pharmacol Exp Ther. 1987 Nov;243(2):487-91.
9 alpha, 11 beta-Prostaglandin F2 (9 alpha, 11 beta-PGF2) is a novel PG formed from PGD2 by the action of 11-ketoreductase which has been shown to exist in the liver, lung and kidneys. 9 alpha, 11 beta-PGF2 has been reported to possess platelet antiaggregatory, vasoconstrictor and bronchoconstrictor properties. To define further the biological activity of 9 alpha, 11 beta-PGF2, with respect to kidney function, studies were conducted in anesthetized male Sprague-Dawley rats prepared for renal clearance measurements. Intravenous infusion of highly-purified 9 alpha, 11 beta-PGF2 (2.5 micrograms/min, n = 9) elevated urine flow (28 +/- 6 microliter/min, P less than .05), urinary sodium/potassium (0.96 +/- 0.31, P less than .05), hematocrit (0.5 +/- 0.3, volumes/100 ml, P less than .05) and urinary sodium excretion (2.3 +/- 1.0 microEq/min). Similar responses but of greater magnitude were obtained with PGF2 alpha (2.5 micrograms/min). Glomerular filtration rate (GFR) and mean arterial pressure (MAP) were unaffected. In contrast, PGD2 (2.5 micrograms/min) resulted in decreases in MAP and concomitant reductions in GFR, urine flow and sodium excretion. Abrupt and pronounced increases in urine flow and sodium excretion were observed on administration of 9 alpha, 11 beta-PGF2 at 7.5 micrograms/min. 9 alpha, 11 beta-PGF2 (2.5 micrograms/min) produced consistent increases in urine flow and the excretion of sodium and chloride in rats treated with meclofenamate, 2 mg/kg/hr i.v., indicating that these responses were not dependent on endogenous PG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
9α,11β-前列腺素F2(9α,11β-PGF2)是一种由11-酮还原酶作用于PGD2形成的新型前列腺素,该酶已被证明存在于肝脏、肺和肾脏中。据报道,9α,11β-PGF2具有血小板抗聚集、血管收缩和支气管收缩特性。为了进一步确定9α,11β-PGF2对肾功能的生物活性,我们对准备进行肾脏清除率测量的麻醉雄性Sprague-Dawley大鼠进行了研究。静脉输注高纯度的9α,11β-PGF2(2.5微克/分钟,n = 9)可使尿流量增加(28±6微升/分钟,P<0.05)、尿钠/钾比值增加(0.96±0.31,P<0.05)、血细胞比容增加(0.5±0.3,体积/100毫升,P<0.05)以及尿钠排泄增加(2.3±1.0微当量/分钟)。用PGF2α(2.5微克/分钟)也得到了类似但程度更大的反应。肾小球滤过率(GFR)和平均动脉压(MAP)未受影响。相比之下,PGD2(2.5微克/分钟)可导致MAP降低,并伴随GFR、尿流量和钠排泄减少。当以7.5微克/分钟的剂量给予9α,11β-PGF2时,观察到尿流量和钠排泄突然且显著增加。在以2毫克/千克/小时静脉注射甲氯芬那酸治疗的大鼠中,9α,11β-PGF2(2.5微克/分钟)可使尿流量以及钠和氯的排泄持续增加,这表明这些反应不依赖于内源性前列腺素的合成。(摘要截断于250字)