脑一氧化氮合酶和盐敏感性高血压

Brain Nitric Oxide Synthase and Salt Sensitive Hypertension

目的：本工作探讨了在不同盐摄取的条件下，脑一氧化氮合酶（ｂｒａｉｎ ｎｉｔｒｉｃ ｏｘｉｄｅ ｓｙｎｔｈａｓｅ， ｂ Ｎ Ｏ Ｓ）对 Ｄａｈｌ 盐敏感（ Ｓ）及 Ｄａｈｌ盐不敏感（ Ｒ）大鼠的血液动力学、血浆肾素活性（ｐｌａｓｍ ａ ｒｅｎｉｎ ａｃｔｉｖｉｔｙ， Ｐ Ｒ Ａ）、肾小球滤过率（ｇｌｕｍ ｅｒｉｌａｒ ｆｉｌ┐ｔｒａｔｉｏｎ ｒａｔｅ， Ｇ Ｆ Ｒ）及有效肾血浆流量（ｅｆｆｅｃｔｉｖｅ ｒｅｎａｌｐｌａｓｍ ａ ｆｌｏｗ ， Ｅ Ｒ Ｐ Ｆ）等的影响。 方法：７ 周～８ 周龄的 Ｓ及 Ｒ大鼠经股静脉导管给予低盐（０．８７ ｍ ｍ ｏｌ／ｄ）及高盐（２０．６ ｍ ｍ ｏｌ／ｄ）溶液输注，并经与计算机系统相联的主动脉导管记录血液动力学等的变化。所有动物在经 ５ 天的对照观察后，其中部分动物在低盐或高盐溶液中加入ｂ Ｎ Ｏ Ｓ特异抑制剂 ７┐ｎｉｔｒｏｉｎｄａｚｏｌｅ （７┐ Ｎ Ｉ， １．６７ ｍ ｇ／ｋｇ／ｈ）， 继续观察 ５ 天。 结果：单纯低盐及高盐输注的 Ｒ 大鼠，其血压无显著变化，同时给予高盐及 ７┐ Ｎ Ｉ输注的大鼠，其血压较对照期间大幅上升（１２０±６％ ）。同样，在给予高盐及高盐＋ ７┐ Ｎ Ｉ输注的 Ｓ大鼠，其血压亦分别较对照期间上升了 １?

Aim:The goal of this study was to determine the role of brain nitric oxide synthase (bNOS) in the arterial pressure, renal hemodynamic and renal excretory changes in Dahl salt resistant(R) and salt sensitive(S) rats during changes in sodium intake.\ Methods:Fifty three Dahl R and S rats of 7～8 weeks of age with arterial and venous catheters instrumented were subjected to low (0.87 mmol/d) or high (20.6 mmol/d) Na intake. Measurements were made during a 5 day control period followed by a 5 day period of bNOS inhibition with iv 7 nitroindazole (7NI, 1.67 mg·kg -1 /h) or vehicle infusion. Mean arterial pressure increased significantly to 120±6 % control in the R high Na and 7NI rats. \ Results:In R rats either high or low salt intake caused little change in mean BP,while high salt intake plus 7NI increases mean BP 120±6% compared to that in control period. High salt intaked and high salt plus 7NI increased mean BP 110±2% and 114±3% in S rats,respectively. 7NI didn't change slightly( P >0.05) in GFR, effective renal plasma flow, urinary Na excretion or urine volume. However, plasma renin activity decreased significantly in R and S rats on low Na intake +7NI. The data demonstrate that the highly salt resistant Dahl R rat became salt sensitive during bNOS inhibition with 7NI. However, the arterial pressure of the S rat was not affected by 7NI. \ Conclusion: That the nitric oxide produced by bNOS in the Dahl R rat normally helps to prevent salt sensitive hypertension and that low functional levels of bNOS in the S rat may contribute to its salt sensitivity.