Gerber J G, Keller R T, Nies A S
Circ Res. 1979 Jun;44(6):796-9. doi: 10.1161/01.res.44.6.796.
We compared the ability of the vasodilator prostaglandins PGI2, PGE2, and 13,14-dihydro PGE2 to release renin when infused into the denervated, nonfiltering canine kidney in vivo. Papaverine was used as a nonprostaglandin vasodilator. All the prostaglandins tested were capable of stimulating renin secretion, with the scale of potency being 13,14-dihydro PGE2 greater than PGI2 greater than PGE2; papaverine had no effect on renin secretion. These results indicate that both PGE2 and PGI2 can stimulate renin secretion but that vasodilation per se is not a stimulus. 13,14-Dihydro PGE2 was included because it is a poorer substrate than PGE2, both for transport into cells and catabolism to inactive products, but has comparable potency to PGE2 when tested in systems with limited ability to catabolize PGE2. The fact that 13,14-dihydro PGE2 was the most potent prostaglandin tested suggests that the effects of PGE2 in our system are reduced by the kidneys' recognized ability to extract and catabolize PGE2. Since PGI2 is less avidly metabolized than PGE2 by the kidney, the differences in observed potency between PGE2 and PGI2 could be largely the result of differences in renal catabolism of the two prostaglandins rather than differences in intrinsic potency. Therefore, both PGE2 and PGI2 are candidates for the endogenous prostaglandin responsible for stimulating renin secretion.
我们比较了血管舒张性前列腺素前列环素(PGI2)、前列腺素E2(PGE2)和13,14-二氢前列腺素E2在体内注入去神经支配、无滤过功能的犬肾时释放肾素的能力。罂粟碱用作非前列腺素血管舒张剂。所有测试的前列腺素均能够刺激肾素分泌,效力大小顺序为13,14-二氢前列腺素E2大于前列环素大于前列腺素E2;罂粟碱对肾素分泌无影响。这些结果表明,PGE2和前列环素均可刺激肾素分泌,但血管舒张本身并非刺激因素。纳入13,14-二氢前列腺素E2是因为它对于转运进入细胞以及分解代谢为无活性产物而言,均是比PGE2更差的底物,但在对PGE2分解代谢能力有限的系统中进行测试时,其效力与PGE2相当。13,14-二氢前列腺素E2是所测试的最有效的前列腺素,这一事实表明,在我们的系统中,PGE2的作用因肾脏公认的对PGE2的提取和分解代谢能力而降低。由于肾脏对前列环素的代谢不如对PGE2那样活跃,PGE2和前列环素之间观察到的效力差异可能很大程度上是这两种前列腺素肾脏分解代谢差异的结果,而非内在效力差异的结果。因此,PGE2和前列环素均有可能是负责刺激肾素分泌的内源性前列腺素。