Kitami Y, Okura T, Wakamiya R, Marumoto K, Iwata T, Hiwada K
Second Department of Internal Medicine, Ehime University School of Medicine, Japan.
Blood Press Suppl. 1992;3:12-6.
Regulation of the gene expression of type-1 angiotensin II receptor (AT1) by treatment with manidipine, a calcium channel blocker, or delapril, an angiotensin converting enzyme inhibitor, for one week was assessed in the adrenal gland, heart, kidney, and brain from spontaneously hypertensive rats (SHR). Tissue AT1 receptor messenger RNA (mRNA) content was measured by reverse transcriptase-polymerase chain reaction. Treatment with manidipine (3 mg/kg/day) or delapril (30 mg/kg/day) lowered systolic blood pressure (SBP) significantly (p < 0.01) (delta SBP; -73 mmHg or -67 mmHg, respectively). Although delapril markedly increased plasma renin activity (PRA), manidipine did not alter PRA. AT1 receptor mRNA content in the adrenal gland was significantly (p < 0.01) decreased by treatment with manidipine or delapril. In contrast, cardiac AT1 receptor mRNA content was significantly (p < 0.01) increased by treatment with either agent. There was no significant change in renal and brain AT1 receptor mRNA contents. These findings suggest that although the expression of AT1 receptor gene depends on the circulating renin-angiotensin system (RAS), it is regulated independently in a tissue-specific manner via the local RAS in each tissue of SHR.
在自发性高血压大鼠(SHR)的肾上腺、心脏、肾脏和脑中,评估了用钙通道阻滞剂马尼地平或血管紧张素转换酶抑制剂地拉普利治疗一周对1型血管紧张素II受体(AT1)基因表达的调节作用。通过逆转录聚合酶链反应测量组织AT1受体信使核糖核酸(mRNA)含量。用马尼地平(3毫克/千克/天)或地拉普利(30毫克/千克/天)治疗可显著降低收缩压(SBP)(p<0.01)(收缩压变化量分别为-73毫米汞柱或-67毫米汞柱)。尽管地拉普利显著增加了血浆肾素活性(PRA),但马尼地平并未改变PRA。用马尼地平或地拉普利治疗可使肾上腺中AT1受体mRNA含量显著降低(p<0.01)。相反,用这两种药物治疗均可使心脏AT1受体mRNA含量显著增加(p<0.01)。肾脏和脑中的AT1受体mRNA含量没有显著变化。这些发现表明,尽管AT1受体基因的表达依赖于循环肾素-血管紧张素系统(RAS),但在SHR的每个组织中,它通过局部RAS以组织特异性方式独立调节。