Scharschmidt L A, Lianos E, Dunn M J
Fed Proc. 1983 Nov;42(14):3058-63.
The glomerulus is a dynamic structure capable of regulating the glomerular filtration rate (GFR) by mesangial contraction, thereby decreasing Kf. The mesangium contracts in response to angiotensin II (AII) and arginine vasopressin (AVP), both of which are potent stimuli of vasodilatory prostaglandin (PG) production. We studied interactions among these opposing factors in glomeruli. Normal rat glomeruli synthesized PGF2 alpha greater than PGE2 greater than 6-keto-PGF1 alpha = thromboxane (Tx) B2. Rat glomerular epithelial and mesangial cells, although capable of producing these four cyclooxy-genase end products, responded to AVP and AII stimulation with a preferential increase of PGE2, which suggests an intraglomerular feedback system between constrictor and dilator factors. Whole glomeruli, when incubated in AII, decreased in size, with a maximum decrement of surface area at 10(-10) M AII. In these glomerular contraction studies, preincubation with either arachidonate or PGE2 decreased the contractile response to AII, whereas PG inhibition enhanced the glomerular contractile response. Stable endoperoxide analogs also contracted glomeruli. In the acute phase of nephrotoxic serum nephritis (NSN) there were marked increments in glomerular production of TxA2, which correlated temporally with decrements of GFR and filtration fraction. Inhibition of TxA2 synthesis normalized GFR and filtration fraction 1-3 h after induction of NSN. These studies suggest not only an important physiological feedback role of vasodilatory PGs, as modulators of AII-induced glomerular contraction, but also a direct mesangial contractile effect of the arachidonate metabolite TxA2.
肾小球是一种动态结构，能够通过系膜收缩来调节肾小球滤过率（GFR），从而降低滤过系数（Kf）。系膜会对血管紧张素II（AII）和精氨酸加压素（AVP）产生收缩反应，而这两种物质都是血管舒张性前列腺素（PG）生成的强效刺激物。我们研究了肾小球中这些相互对立因素之间的相互作用。正常大鼠肾小球合成的前列腺素F2α（PGF2α）大于前列腺素E2（PGE2），大于6-酮-前列腺素F1α（6-keto-PGF1α）=血栓素（Tx）B2。大鼠肾小球上皮细胞和系膜细胞虽然能够产生这四种环氧化酶终产物，但对AVP和AII刺激的反应是PGE2优先增加，这表明在收缩因子和舒张因子之间存在肾小球内反馈系统。完整的肾小球在AII中孵育时会缩小，在10^(-10)M AII时表面积减少最大。在这些肾小球收缩研究中，预先用花生四烯酸或PGE2孵育可降低对AII的收缩反应，而PG抑制则增强肾小球收缩反应。稳定的内过氧化物类似物也会使肾小球收缩。在肾毒性血清性肾炎（NSN）的急性期，肾小球血栓素A2（TxA2）的生成显著增加，这与GFR和滤过分数的降低在时间上相关。抑制TxA2合成可使NSN诱导后1 - 3小时的GFR和滤过分数恢复正常。这些研究不仅表明血管舒张性PG作为AII诱导的肾小球收缩的调节剂具有重要的生理反馈作用，还表明花生四烯酸代谢产物TxA2具有直接的系膜收缩作用。
