Meyer M, Richter R, Forssmann W G
Niedersächsisches Institut für Peptid-Forschung (IPF), Hannover, Germany.
Eur J Med Res. 1998 Feb 21;3(1-2):103-110.
Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also profit from URO treatment, as it increases stroke volume and PCWP. Moreover, preliminary results from recent studies indicate that URO may also be effective in patients suffering from hepato-renal syndrome.
利钠肽（NP）构成了具有重大临床影响的激素系统。本报告涉及尿舒张素（URO），一种A型肾利钠肽。从A型NP基因转录出前激素原的信使核糖核酸，在心脏和肾脏中进行转录。心脏前激素CDD/ANP-1-126在心房合成，并在胞吐过程中加工形成循环激素CDD/ANP-99-126。URO（CDD/ANP 95-126）是同一基因的产物，但在肾脏中经过不同的加工，仅在尿液中检测到。生理上，URO以旁分泌方式发挥作用。从远端肾小管细胞释放到肾小管腔后，URO与集合管中的管腔受体（NPR-A）结合，导致依赖环磷酸鸟苷（cGMP）的信号转导。cGMP生成后与阿米洛利敏感钠通道相互作用，诱导利尿和利钠作用。通过这种方式，URO在生理上调节体液平衡和钠稳态。此外，URO的排泄和利钠作用又取决于多种生理状态，如直接受钠稳态的影响。药理学上，静脉注射低剂量的URO显示出强烈的利尿和利钠作用以及较低的降压作用。药理剂量引起的肾脏、肺部和心血管效应表明，URO是几种相关疾病的潜在药物。临床试验对各种临床适应症显示出有希望的结果。然而，在少数患者的初步试验中，心脏和肝脏移植后急性肾损伤患者血液透析/血液滤过的减少，未得到多中心II期研究的证实。相比之下，在这种临床情况下预防性使用URO的数据表明患者的预后更好。此外，对哮喘患者的治疗显示URO对肺功能有令人信服的有益作用。充血性心力衰竭患者也可能从URO治疗中获益，因为它增加了心输出量和肺毛细血管楔压。此外，最近研究的初步结果表明，URO对肝肾综合征患者也可能有效。
