Tamura K, Chiba E, Yokoyama N, Sumida Y, Yabana M, Tamura N, Takasaki I, Takagi N, Ishii M, Horiuchi M, Umemura S
Department of Internal Medicine II, Yokohama City University School of Medicine, Japan.
J Hypertens. 1999 Jan;17(1):81-9. doi: 10.1097/00004872-199917010-00013.
The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats.
Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis.
Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet.
These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.
组织肾素 - 血管紧张素系统和细胞外基质参与高血压诱导的心血管肥大和重塑。在本研究中，我们检测了近交系达尔伊瓦伊盐敏感和盐抵抗大鼠中组织肾素 - 血管紧张素系统和纤连蛋白的基因表达。
八对6周龄雄性达尔伊瓦伊盐敏感和盐抵抗大鼠分别给予低或高盐饮食（分别为0.3%或8%氯化钠）4周。通过放射免疫测定法测量循环肾素 - 血管紧张素系统的活性，并通过Northern印迹分析检测组织血管紧张素原、血管紧张素II 1型受体（AT1）和纤连蛋白的基因表达。
盐负荷显著升高盐敏感大鼠的血压，并导致心血管肥大和肾硬化。盐敏感大鼠的循环肾素 - 血管紧张素系统活性低于喂食低盐饮食的盐抵抗大鼠，盐负荷降低了盐抵抗大鼠的这些活性，但对盐敏感大鼠没有影响。在盐抵抗大鼠中，盐负荷增加了肾脏、心脏和主动脉血管紧张素原、AT1和纤连蛋白信使（m）RNA的表达，但主动脉纤连蛋白mRNA表达除外。相反，在盐敏感大鼠中，盐负荷刺激了心脏纤连蛋白以及主动脉血管紧张素原、AT1和纤连蛋白mRNA的表达。此外，当两种品系都喂食高盐饮食时，盐敏感大鼠心脏和主动脉纤连蛋白mRNA水平高于盐抵抗大鼠。
这些结果表明，达尔伊瓦伊盐敏感和盐抵抗大鼠中组织血管紧张素原、AT1和纤连蛋白mRNA的表达调控不同，并表明盐介导的高血压独立于组织肾素 -血管紧张素系统激活心脏纤连蛋白基因，并通过组织肾素 -血管紧张素系统的激活刺激主动脉纤连蛋白基因。
