Sällström Johan, Carlström Mattias, Jensen Boye L, Skøtt Ole, Brown Russell D, Persson A Erik G
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Am J Hypertens. 2008 Jan;21(1):111-6. doi: 10.1038/ajh.2007.16.
Nitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodium loads.
Blood pressure and heart rate were measured telemetrically and assessed during periods of physical activity and inactivity. Urinary solute excretion was measured by metabolism cages and plasma renin concentration (PRC) was determined by radioimmunoassay; all in nNOS knockout (nNOS(-/-)) and wild-type (nNOS(+/+)) mice after 10 days of low (0.01% NaCl) and high (4% NaCl) sodium diets.
The resting heart rate was reduced in nNOS(-/-) mice, but the two genotypes had similar blood pressure during the low (nNOS(+/+) 104 +/- 2 mm Hg; nNOS(-/-) 103 +/- 2 mm Hg) and high (nNOS(+/+) 107 +/- 3 mm Hg; nNOS(-/-) 108 +/- 2 mm Hg) sodium diets. During the high sodium diet, PRC did not differ between the genotypes (nNOS(+/+) 743 +/- 115 10(-5) Goldblatt units; nNOS(-/-) 822 +/- 63 10(-5) Goldblatt units), but during the low sodium diet, nNOS(-/-) mice failed to increase PRC (nNOS(+/+) 2164 +/- 220 10(-5) Goldblatt units; nNOS(-/-) 907 +/- 101 10(-5) Goldblatt units) and renal renin mRNA. On the low sodium diet, nNOS(-/-) mice also showed increased urine flow rate and osmolar excretion, observations not made during a high sodium diet.
Our results show that nNOS is necessary for stimulation of renin in response to sodium restriction. Furthermore, nNOS(-/-) mice are normotensive, and their blood pressure responds normally to an increased dietary sodium intake, indicating that nNOS deficiency does not cause salt-sensitive hypertension.
一氧化氮缺乏与高血压的发生有关，但目前其机制尚不清楚。本研究旨在进一步阐明神经元型一氧化氮合酶（nNOS）在不同钠负荷情况下对血压调节及肾素释放的作用。
通过遥测法测量血压和心率，并在活动期和非活动期进行评估。使用代谢笼测量尿溶质排泄，采用放射免疫分析法测定血浆肾素浓度（PRC）；所有测量均在给予低钠（0.01% NaCl）和高钠（4% NaCl）饮食10天后的nNOS基因敲除（nNOS(-/-)）小鼠和野生型（nNOS(+/+)）小鼠中进行。
nNOS(-/-)小鼠静息心率降低，但在低钠（nNOS(+/+) 104±2 mmHg；nNOS(-/-) 103±2 mmHg）和高钠（nNOS(+/+) 107±3 mmHg；nNOS(-/-) 108±2 mmHg）饮食期间，两种基因型的血压相似。在高钠饮食期间，各基因型之间的PRC无差异（nNOS(+/+) 743±115×10⁻⁵ Goldblatt单位；nNOS(-/-) 822±63×10⁻⁵ Goldblatt单位），但在低钠饮食期间，nNOS(-/-)小鼠未能增加PRC（nNOS(+/+) 2164±220×10⁻⁵ Goldblatt单位；nNOS(-/-) 907±101×10⁻⁵ Goldblatt单位）及肾素mRNA水平。在低钠饮食时，nNOS(-/-)小鼠还表现出尿流率和渗透排泄增加，而在高钠饮食期间未观察到这些现象。
我们的结果表明，nNOS是钠限制时刺激肾素分泌所必需的。此外，nNOS(-/-)小鼠血压正常，其血压对饮食中钠摄入量增加的反应也正常，这表明nNOS缺乏不会导致盐敏感性高血压。
