Wood P A, Hamm D A, Chen P Y, Sanders P W
Department of Comparative Medicine, Univeristy of Alabama at Birmingham 35294, USA.
Mol Genet Metab. 1998 May;64(1):80-3. doi: 10.1006/mgme.1998.2696.
Previous studies by our group demonstrated a striking relationship among arginine, nitric oxide production, and salt-sensitive hypertension in the Dahl/Rapp rat. We hypothesized that enzymes of the urea cycle may be involved in this process. We specifically examined the activities of liver and kidney argininosuccinate synthetase (AS), because this enzyme is an essential step of arginine synthesis and a likely control point. We found that salt-sensitive (S) rats on a high-salt diet developed hypertension without change in plasma concentrations of arginine, citrulline, and ornithine. Baseline plasma concentrations of these amino acids were the same in rats of all three genotypes: Sprague-Dawley (SD), S, and salt-resistant (R) Dahl/Rapp rats. In contrast, R rats on the high-salt diet remained normotensive coincidentally with elevated levels of arginine and ornithine, as compared to normotensive R rats on low-salt diet with no changes in amino acid concentrations. S rats on high-salt diet became hypertensive coincidentally with no changes in amino acid concentrations. None of the rat groups had significantly different activity of liver of kidney AS coincidental with the salt in the diet and the changes in amino acid concentrations found in the R rats. Thus, given the lack of alteration in plasma concentrations of the urea cycle amino acids of arginine, citrulline, and ornithine in S rats, genes of the urea cycle/arginine synthesis are unlikely to be involved in salt-sensitive hypertension in this strain. The mechanism of increased plasma arginine and ornithine concentrations in R rats was not determined, but was not related to AS activity.
我们小组之前的研究表明，在 Dahl/Rapp 大鼠中，精氨酸、一氧化氮生成与盐敏感性高血压之间存在显著关系。我们推测尿素循环的酶可能参与了这一过程。我们特别研究了肝脏和肾脏中精氨琥珀酸合成酶（AS）的活性，因为该酶是精氨酸合成的关键步骤，也是一个可能的控制点。我们发现，高盐饮食的盐敏感性（S）大鼠出现了高血压，但其血浆中精氨酸、瓜氨酸和鸟氨酸的浓度没有变化。所有三种基因型的大鼠，即 Sprague-Dawley（SD）、S 和盐抵抗（R）Dahl/Rapp 大鼠，这些氨基酸的基线血浆浓度是相同的。相比之下，与低盐饮食且氨基酸浓度无变化的血压正常的 R 大鼠相比，高盐饮食的 R 大鼠血压正常，同时精氨酸和鸟氨酸水平升高。高盐饮食的 S 大鼠出现高血压，而氨基酸浓度没有变化。没有一组大鼠的肝脏或肾脏 AS 活性与饮食中的盐分以及 R 大鼠中发现的氨基酸浓度变化有显著差异。因此，鉴于 S 大鼠血浆中尿素循环氨基酸精氨酸、瓜氨酸和鸟氨酸的浓度没有改变，尿素循环/精氨酸合成的基因不太可能参与该品系的盐敏感性高血压。R 大鼠血浆中精氨酸和鸟氨酸浓度升高的机制尚未确定，但与 AS 活性无关。
