Tamura K, Yokoyama N, Sumida Y, Fujita T, Chiba E, Tamura N, Kobayashi S, Kihara M, Murakami K, Horiuchi M, Umemura S
Department of Dermatology, Yokohama City University School of Medicine, Yokohama 236, Japan.
J Endocrinol. 1999 Mar;160(3):401-8. doi: 10.1677/joe.0.1600401.
This study examined whether type 1 angiotensin II receptor (AT1) and angiotensin-converting enzyme (ACE) mRNAs are regulated during dietary salt loading in angiotensinogen gene-knockout (Atg-/-) mice which are genetically deficient in endogenous production of angiotensin II. Wild-type (Atg+/+) and Atg-/- mice were fed a normal-salt (0.3% NaCl) or a high-salt (4% NaCl) diet for 2 weeks. The mRNA levels were measured by Northern blot analysis. In Atg+/+ mice, concentrations of plasma angiotensin peptides were decreased by salt loading, whereas the treatment increased the brainstem, cardiac, pulmonary, renal cortex, gastric and intestinal AT1 mRNA levels. Salt loading also enhanced renal cortex ACE mRNA levels in Atg+/+ mice. Although plasma angiotensin peptides and urinary aldosterone excretion were not detected in Atg-/- mice, salt loading increased blood pressure in Atg-/- mice. In Atg-/- mice, pulmonary, renal cortex, gastric and intestinal AT1, and renal cortex and intestinal ACE mRNA levels were higher than those in Atg+/+ mice. However, salt loading upregulated AT1 mRNA expression only in the liver of Atg-/- mice, and the treatment did not affect ACE mRNA levels in Atg-/- mice. Furthermore, although the levels of ACE enzymatic activity showed the same trend with the ACE mRNA levels in the lung, renal cortex and intestine of both Atg-/- and Atg+/+ mice, the results of radioligand binding assay showed that cardiac expression of AT1 protein was regulated differently from AT1 mRNA expression both in Atg-/- and Atg+/+ mice. Thus, expression of AT1 and ACE is regulated by salt loading in a tissue-specific manner that appears to be mediated, at least partly, by a mechanism other than changes in the circulating or tissue levels of angiotensin peptides.
本研究检测了在血管紧张素原基因敲除（Atg-/-）小鼠（其体内内源性血管紧张素II生成存在基因缺陷）的饮食盐负荷期间，1型血管紧张素II受体（AT1）和血管紧张素转换酶（ACE）的mRNA是否受到调控。野生型（Atg+/+）和Atg-/-小鼠分别喂食正常盐（NaCl 0.3%）或高盐（NaCl 4%）饮食2周。通过Northern印迹分析测量mRNA水平。在Atg+/+小鼠中，盐负荷降低了血浆血管紧张素肽的浓度，而该处理增加了脑干、心脏、肺、肾皮质、胃和肠道的AT1 mRNA水平。盐负荷也提高了Atg+/+小鼠肾皮质ACE mRNA水平。虽然在Atg-/-小鼠中未检测到血浆血管紧张素肽和尿醛固酮排泄，但盐负荷使Atg-/-小鼠血压升高。在Atg-/-小鼠中，肺、肾皮质、胃和肠道的AT1以及肾皮质和肠道的ACE mRNA水平高于Atg+/+小鼠。然而，盐负荷仅上调了Atg-/-小鼠肝脏中的AT1 mRNA表达，且该处理未影响Atg-/-小鼠的ACE mRNA水平。此外，虽然在Atg-/-和Atg+/+小鼠的肺、肾皮质和肠道中，ACE酶活性水平与ACE mRNA水平呈现相同趋势，但放射性配体结合试验结果表明，在Atg-/-和Atg+/+小鼠中，心脏AT1蛋白的表达与AT1 mRNA表达的调控方式不同。因此，AT1和ACE的表达以组织特异性方式受到盐负荷的调控，这种调控似乎至少部分由一种不同于血管紧张素肽循环或组织水平变化的机制介导。
