Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, Yasukawa H, Iwami G, Okuda S, Imaizumi T
Department of Internal Medicine III, Kurume University School of Medicine, Fukuoka, Japan.
Hypertension. 1997 Jan;29(1 Pt 2):242-7. doi: 10.1161/01.hyp.29.1.242.
NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P < .01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P < .01), did not change urinary NOx excretion, and increased UADMA (P < .01). There was a significant (r = .65, P < .01) correlation between UADMA and the level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and ADMA and renal dimethylargininase content were comparable among them. These results may suggest that in Dahl salt-resistant rats, blood pressure is kept constant during high-salt intake, possibly due to the compensatory increased production of NO, and that in Dahl salt-sensitive rats, high-salt intake increases the production of ADMA, attenuates the compensatory increases in NO, and increases blood pressure. These results also suggest that the systemic production of ADMA is not dependent on renal dimethylargininase. SHR had significantly greater urinary NOx excretion (P < .05) and smaller UADMA than Wistar-Kyoto rats (P < .05), and UADMA was inversely correlated with their mean arterial pressure (r =.64, P < .05). In conclusion. ADMA, independently of the renal dimethylargininase content, may play a role in the pathogenesis in Dahl salt-sensitive hypertensive rats but not in SHR.
非对称二甲基精氨酸（ADMA）是一种内源性合成的一氧化氮（NO）合酶抑制剂，具有强大的升压/血管收缩作用。二甲基精氨酸酶将ADMA代谢为L-瓜氨酸，在决定ADMA的体内水平方面起关键作用。为了研究ADMA在高血压发病机制中的作用，我们测量了 Dahl 盐敏感型高血压大鼠和自发性高血压大鼠（SHR）中ADMA的24小时尿排泄量（UADMA）以及硝酸盐/亚硝酸盐（NOx）。在Dahl盐抵抗大鼠中，与低盐饮食（0.3% NaCl）相比，高盐饮食（8% NaCl）不会升高血压，但会增加尿NOx（P <.01），而UADMA没有变化。相反，在Dahl盐敏感大鼠中，高盐饮食会升高血压（P <.01），不改变尿NOx排泄量，但会增加UADMA（P <.01）。在Dahl盐敏感大鼠中，UADMA与血压水平之间存在显著相关性（r =.65，P <.01）。它们之间的血浆NOx和ADMA水平以及肾脏二甲基精氨酸酶含量相当。这些结果可能表明，在Dahl盐抵抗大鼠中，高盐摄入期间血压保持恒定，可能是由于NO的代偿性增加产生；而在Dahl盐敏感大鼠中，高盐摄入会增加ADMA的产生，减弱NO的代偿性增加，并升高血压。这些结果还表明，ADMA的全身产生不依赖于肾脏二甲基精氨酸酶。与Wistar-Kyoto大鼠相比，SHR的尿NOx排泄量显著更高（P <.05），UADMA更小（P <.05），并且UADMA与其平均动脉压呈负相关（r =.64，P <.05）。总之，独立于肾脏二甲基精氨酸酶含量，ADMA可能在Dahl盐敏感型高血压大鼠的发病机制中起作用，但在SHR中不起作用。
