Oishi T, Ogura T, Yamauchi T, Harada K, Ota Z
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Regul Pept. 1996 Apr 23;62(2-3):89-95. doi: 10.1016/0167-0115(95)00166-2.
To determine whether growth factors in the glomerulus are induced in the renin suppressed hypertensive model, we examined the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)-beta 1 and angiotensin II type 1 (AT1) receptors in the glomeruli of deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats (DOCA-treated rats). We also examined the effects of treatment with cilazapril, an angiotensin I-converting enzyme inhibitor (ACEI), and L-158,809, an AT1 receptor antagonist, on these expressions in DOCA-treated rats. We administered oral 10 mg/kg of cilazapril (CILAZA group) and 1 mg/kg of L-158,809 (L158 group) to DOCA-treated rats daily. Systolic blood pressure in the two groups was not decreased compared with that in DOCA-treated rats given saline. The mRNA expressions were examined using reverse transcriptase polymerase chain reaction (RT-PCR) methods. The mRNA expressions of these genes were higher in DOCA-treated rats than in age-matched control rats. After treatment with these agents for 4 weeks, the mRNA expressions of growth factors were suppressed in both the CILAZA and L158 groups. Mesangial expansion and cell proliferation observed in DOCA-treated rats were suppressed in both the CILAZA and L158 groups. Decreases in the size of the glomerulus were observed only in the CILAZA group. These findings suggested that suppression of growth factors and glomerular proliferative changes of these agents are mediated by blocking tissue renin-angiotensin system (RAS) in the renin-suppressed model.
为了确定肾小球中的生长因子是否在肾素抑制性高血压模型中被诱导，我们检测了醋酸脱氧皮质酮（DOCA）-盐处理的高血压大鼠（DOCA处理大鼠）肾小球中血小板衍生生长因子（PDGF）B链、转化生长因子（TGF）-β1和血管紧张素II 1型（AT1）受体的mRNA表达。我们还研究了用血管紧张素I转换酶抑制剂（ACEI）西拉普利和AT1受体拮抗剂L-158,809处理对DOCA处理大鼠这些表达的影响。我们每天给DOCA处理的大鼠口服10 mg/kg西拉普利（CILAZA组）和1 mg/kg L-158,809（L158组）。与给予生理盐水的DOCA处理大鼠相比，两组的收缩压均未降低。使用逆转录聚合酶链反应（RT-PCR）方法检测mRNA表达。这些基因的mRNA表达在DOCA处理大鼠中高于年龄匹配的对照大鼠。用这些药物处理4周后，CILAZA组和L158组的生长因子mRNA表达均受到抑制。CILAZA组和L158组均抑制了DOCA处理大鼠中观察到的系膜扩张和细胞增殖。仅在CILAZA组中观察到肾小球大小减小。这些发现表明，在肾素抑制模型中，这些药物对生长因子的抑制和肾小球增殖性变化是通过阻断组织肾素-血管紧张素系统（RAS）介导的。
