The investigation of molecular biological mechanisms and therapy of refractory renal edema.

本研究旨在探讨难治性肾水肿的发病机制和治疗方法。我们关注的是V1a和V2加压素(ADH)受体。我们已经报道V2受体定位于远端肾单位段的基底外侧膜。因此，我们首先研究了V1a受体在肾内的定位。结果表明，V1a受体位于肾小球和集合管的管腔膜上。其次，探讨了V2受体(V2R)在内髓集合管(IMCD)中的表达机制。已知V2R mRNA在脱水时下调。然而，众所周知，加压素和高渗透压在脱水时都会增加，在体外刺激V2R mRNA的表达。脱水对V2R基因表达有一定的抑制作用。其中一种是前列腺素E2(PGE2)。已知PGE2可减少集合管中依赖ADH的cAMP的生成。PGE2可抑制ADH和高渗刺激的V2R基因表达。因此，PGE2生成的增加似乎抑制了脱水时V2R mRNA的表达。我们仍在研究PGE2的作用，以了解利尿的机制。我们研究的最终目标是将我们的知识用于治疗肾性水肿。

This study was designed to investigate the mechanisms and therapy of refractory renal edema. We have focused on V1a and V2 vasopressin (ADH) receptors. WE have already reported the V2 receptor is localized in basolateral membrane of distal nephron segments. Therefore, we first investigated intranephron localization of V1a receptor. The results showed that V1a receptor is located in glomeruli and in luminal membrane of collecting ducts.Next, the mechanisms of V2 receptor (V2R) mRNA expression in inner medullary collecting ducts (IMCD) were investigated. V2R mRNA is known to downregulate in dehydration. However, vasopressin and hyperosmolality, both are known to increase in dehydration, stimulated V2R mRNA expression in vitro. There is some inhibitory factor on V2R mRNA expression in dehydration. One of the canditate is prostaglandin E2 (PGE2). PGE2 is known to decrease ADH-dependent cAMP generation in collecting ducts. PGE2 inhibited ADH- and hyperosmolality-stimulated V2R mRNA expression. Thus, increased PGE2 generation seems to inhibit V2R mRNA expression in dehydration. We are still investigating the role of PGE2 to know the mechanisms of diuresis. The final goal of our study is to use our knowledge for the therapy of renal edema.