Jackson E K, Herzer W A, Zimmerman J B, Branch R A, Oates J A, Gerkens J F
J Pharmacol Exp Ther. 1981 Jan;216(1):24-7.
Several studies indicate that prostaglandin (PG) I2 is involved in the control of renin release. This investigation was performed to determine if the active possible metabolite of PGI2, 6-keto-PGE1, is also a renin secretagogue. The relative potencies of PGI2, 6-keto-PGE1 and 6-keto-PGF1 alpha on renin secretion rate (RSR) and renal blood flow (RBF) were assessed in nonfiltering, beta adrenoreceptor blocked kidneys of seven anesthetized dogs. Intrarenal infusions of both PGI2 and 6-keto-PGE1 significantly augmented RSR in a dose-related fashion. However, 6-keto-PGE1 was approximately 5 times more potent than PGI2, producing significantly greater increases in RSR at doses from 3 X 10(-9) to 3 X 10(-8 g/kg/min (P < .03). At low infusion rates (less than 3 X 10(-8) g/kg/min), 6-keto-PGE1 enhanced RBF to a greater extent than PGI2. However, with infusion rates of 3 X 10(-8) g/kg/min, these eicosanoides enhanced RBF to an equal extent. Thus, in comparison to PGI2, 6-keto-PGF1 induced a greater increase in RSR for equivalent increases in RBF. 6-keto-PGF 1 alpha had no effect on either RSR or RBF at any of the doses infused. We conclude that, in the canine kidney, 6-keto-PGE1 is more potent than PGI2 in stimulating the juxtaglomerular cells to secrete renin.
多项研究表明,前列腺素(PG)I2参与肾素释放的调控。本研究旨在确定PGI2的活性可能代谢产物6-酮-PGE1是否也是一种肾素分泌刺激剂。在7只麻醉犬的无滤过、β肾上腺素能受体阻断的肾脏中,评估了PGI2、6-酮-PGE1和6-酮-PGF1α对肾素分泌率(RSR)和肾血流量(RBF)的相对效力。肾内输注PGI2和6-酮-PGE1均以剂量相关方式显著增加RSR。然而,6-酮-PGE1的效力约为PGI2的5倍,在3×10^(-9)至3×10^(-8) g/kg/min的剂量下,RSR的增加显著更大(P <.03)。在低输注速率(小于3×10^(-8) g/kg/min)时,6-酮-PGE1比PGI2更能增强RBF。然而,在3×10^(-8) g/kg/min的输注速率下,这些类花生酸对RBF的增强程度相同。因此,与PGI2相比,6-酮-PGF1在同等程度的RBF增加时诱导了更大的RSR增加。在任何输注剂量下,6-酮-PGF1α对RSR或RBF均无影响。我们得出结论,在犬肾中,6-酮-PGE1在刺激球旁细胞分泌肾素方面比PGI2更有效。