High salt intake and the brain renin–angiotensin system in Dahl salt-sensitive rats
High salt intake and the brain renin–angiotensin system in Dahl salt-sensitive rats
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Dahl 盐敏感大鼠的高盐摄入量与脑肾素-血管紧张素系统
DOI：
10.1097/00004872-200101000-00012
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发表时间：
2001
影响因子：
4.9
通讯作者：
F. Leenen
中科院分区：
文献类型：
--
作者：
Xigeng Zhao;Roselyn A. White;B. Huang;J. V. Van Huysse;F. Leenen
目的评估在盐敏感性高血压的发展过程中以及通过阻断脑哇巴因预防盐敏感性高血压过程中脑肾素-血管紧张素系统活性的变化。方法在第一方案中，观察了4-6周龄和4-9周龄的盐敏感（Dahl S）和盐抵抗（Dahl R）大鼠在常规（120 μmol Na+/g）和高盐（1370 μmol Na +/g）饮食条件下下丘脑和脑桥血管紧张素转换酶（ACE）mRNA和活性以及血管紧张素I和II水平的变化。在方案II中，在Dahl S的下丘脑和脑桥中评估ACE mRNA和活性，所述Dahl S接受常规或高盐脑室内（i. c. v.）Fab片段阻断脑'哇巴因'或γ-球蛋白，并在达尔R高或普通盐。ACE mRNA的定量逆转录聚合酶链反应（RT-PCR）测定和血管紧张素I和II的放射免疫分析后，高效液相色谱。在方案III中，在4-8周龄的常规或高盐摄入的Dahl S和R大鼠中评估了i. c. v.血管紧张素I和i. c. v.缓激肽在i. c. v.卡托普利之前和之后对肾交感神经活动（RSNA）、心率和血压的影响。结果高盐饮食引起Dahl S大鼠血压逐渐升高，但升高幅度明显，而Dahl R大鼠血压无明显变化。Dahl S大鼠在常规盐饮食的下丘脑中显示出小但显著的ACE mRNA增加。在Dahl S大鼠高盐饮食2或5周的ACE mRNA水平显着增加，在下丘脑和脑桥，与Dahl R大鼠的饮食或Dahl S大鼠的常规饮食。经过5周的高盐饮食，ACE mRNA水平在下丘脑的达尔S大鼠几乎高出3倍，在脑桥高出2倍，比达尔R大鼠的饮食或达尔S的常规盐饮食。高盐饮食还增加了Dahl S的下丘脑和脑桥的ACE活性，但对Dahl R没有影响。与ACE活性增加一致，在高盐摄入的Dahl S中，对血管紧张素I的中枢反应明显增强，对缓激肽的中枢反应明显减弱。慢性阻断脑'哇巴因'的i. c. v. Fab片段防止血压，ACE mRNA和活性的增加，在下丘脑和脑桥的高盐摄入量在达尔S大鼠。两组大鼠下丘脑和脑桥中的血管紧张素I水平相似，并且Dahl S和R大鼠的高盐饮食没有引起显着变化。定期盐摄入量的血管紧张素II水平在下丘脑的Dahl S大鼠表现出显着下降相比，Dahl R大鼠定期盐饮食，并在两个品系的脑桥相似。高盐摄入量并没有影响血管紧张素II水平在下丘脑或脑桥在达尔S和R大鼠。结论高盐摄入可增加Dahl S大鼠血压、下丘脑和脑桥ACE表达和活性，但血管紧张素II水平无平行增加。高盐摄入对ACE mRNA和活性的影响似乎是继发于脑“哇巴因”的激活。
Objectives To assess changes in the activity of the brain renin–angiotensin system during (i) the development of salt-sensitive hypertension; and (ii) the prevention of salt-sensitive hypertension by blocking brain ‘ouabain'. Methods In protocol I, angiotensin converting enzyme (ACE) mRNA and activity and angiotensin I and II levels were assessed in the hypothalamus and pons of Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on regular (120 μmol Na+ per g) or high (1370 μmol Na+ per g) salt diet from 4–6 weeks or 4–9 weeks of age. In protocol II, ACE mRNA and activity were assessed in the hypothalamus and pons in Dahl S on regular or high salt treated with intracerebroventricular (i.c.v.) Fab fragments blocking brain ‘ouabain’ or γ-globulins, and in Dahl R on high or regular salt. ACE mRNA was assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and angiotensin I and II by radioimmunoassay after high-performance liquid chromatography. In protocol III, effects of i.c.v. angiotensin I and i.c.v. bradykinin on renal sympathetic nerve activity (RSNA), heart rate and blood pressure before and after i.c.v. captopril were assessed in Dahl S and R rats on regular or high salt intake from 4–8 weeks of age. Results High salt diet caused a gradual, but marked increase in blood pressure in Dahl S but not Dahl R rats. Dahl S rats showed small but significant increases in ACE mRNA in the hypothalamus on regular salt diet. In Dahl S rats on high salt diet for 2 or 5 weeks ACE mRNA levels significantly increased in both hypothalamus and pons, compared with Dahl R rats on either diet or Dahl S rats on regular diet. After 5 weeks of high salt diet, ACE mRNA levels in the hypothalamus in Dahl S rats were almost three-fold higher and in the pons two-fold higher than in Dahl R rats on either diet or Dahl S on regular salt diet. High salt diet also increased ACE activity of the hypothalamus and pons in Dahl S but not Dahl R. Consistent with this increased ACE activity, central responses to angiotensin I were clearly enhanced and to bradykinin markedly diminished in Dahl S on high salt intake. Chronic blockade of brain ‘ouabain’ by i.c.v. Fab fragments prevented the increases in blood pressure, ACE mRNA and activity in the hypothalamus and pons by high salt intake in Dahl S rats. Angiotensin I levels in the hypothalamus and pons were similar in both groups of rats and there were no significant changes caused by high salt diet in Dahl S and R rats. On regular salt intake angiotensin II levels in the hypothalamus of Dahl S rats showed a significant decrease as compared with Dahl R rats on regular salt diet, and were similar in the pons of the two strains. High salt intake did not affect angiotensin II levels in either hypothalamus or pons in Dahl S and R rats. Conclusions These results indicate that high salt intake increases blood pressure, ACE expression and activity in the hypothalamus and pons of Dahl S rats without a parallel increase in angiotensin II levels. Effects of high salt intake on ACE mRNA and activity appear to be secondary to activation of brain ‘ouabain'.
延髓头端腹外侧区是激肽中枢高血压作用的部位。
DOI：
10.1161/01.hyp.23.1.52
发表时间：
1994
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Privitera,PJ;Thibodeaux,H;Yates,P
通讯作者：
Yates,P
卡托普利急性脑室内给药对达尔盐敏感大鼠的抗高血压作用。
影响因子：
5
作者：
Lark,LA;Weyhenmeyer,JA
通讯作者：
Weyhenmeyer,JA
影响因子：
10.8
作者：
Morrell, NW;Danilov, SM;Stenmark, KR
通讯作者：
Stenmark, KR