Harada K, Ogura T, Yamauchi T, Otsuka F, Mimura Y, Hashimoto M, Oishi T, Makino H
Department of Medicine III, Okayama University Medical School, Japan.
Regul Pept. 1998 Apr 24;74(1):11-8. doi: 10.1016/s0167-0115(98)00009-3.
Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.
血管加压素（VP）被认为在肾小球的升压和增殖反应中起重要作用。我们利用自发性高血压大鼠（SHR）模型来确定外源性VP的慢性输注是否会诱导肾小球增殖。使用渗透微型泵，将SHR连续15天输注0.1 ng/kg/min的VP（高剂量VP组）、1.0 ng/kg/min（高剂量VP组）或仅输注溶媒（对照组），并测定组织学改变以及血小板衍生生长因子B链（PDGF-B）和转化生长因子（TGF）-β1 mRNA的表达水平。我们观察到三组大鼠的收缩压、心率、血清电解质、蛋白质和肌酐水平无显著差异，但高剂量VP组的尿量显著减少，尿渗透压显著升高。高剂量VP组和低剂量VP组的肾脏重量显著高于对照组，高剂量VP组的肾小球直径更大。当我们测量这些动物肾小球的系膜损伤评分和细胞密度时，观察到VP剂量依赖性的增殖变化。在免疫荧光研究中，尽管我们未发现三组之间III型、IV型和VI型胶原蛋白、α平滑肌肌动蛋白和PDGF-B的沉积有明显差异，但高剂量VP组的几个肾小球中I型胶原蛋白和TGF-β1增加。逆转录聚合酶链反应（RT-PCR）显示三组大鼠肾小球中PDGF-B mRNA水平无显著差异，但低剂量VP组和高剂量VP组中TGF-β1 mRNA的表达水平显著高于对照组。这些发现表明VP可能促进肾小球增殖，并且VP可能部分通过诱导TGF-β1表达发挥作用。这些结果还提出了阻断VP受体可能对某些形式的肾小球疾病治疗有用的可能性。
