Altered nitric oxide synthase 3 distribution in mesenteric arteries of hypertensive rats
Altered nitric oxide synthase 3 distribution in mesenteric arteries of hypertensive rats
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DOI：
10.1161/hy0202.103286
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发表时间：
2002-02-01
期刊：
影响因子：
8.3
通讯作者：
Pollock, JS
中科院分区：
文献类型：
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作者：
Sullivan, JC;Pollock, DM;Pollock, JS
高盐（HS）饮食和血管紧张素II（Ang II）都与高血压和内皮功能受损的发展有关。我们推测，一氧化氮合酶（NOS）活性的改变或NOS 3蛋白的亚细胞定位可能有助于盐依赖性高血压的内皮功能障碍。为了验证这一假设，研究了两种盐依赖性高血压模型：DOCA-盐和Ang II。对于Ang II高血压，将大鼠分为4组：正常或HS饮食对照组，Ang II灌注正常或HS饮食。分离肠系膜动脉床并在液氮中冷冻。将冷冻的动脉均质化并分离成细胞溶质和颗粒部分。通过测定在不存在和存在NOS抑制剂Nomega-硝基-L-精氨酸的情况下H-3-精氨酸向H-3-瓜氨酸的转化，测定NOS活性。DOCA-盐组动脉细胞液中NOS 3蛋白表达较安慰剂组显著增加，Ang II组和Ang HS组较对照组显著增加。所有组中颗粒部分的NOS 3表达相当。NOS活性（pmol/30分钟/总蛋白）显着增加，从DOCA-盐大鼠动脉的胞质部分相比，安慰剂和Ang HS大鼠相比，对照。NOS活性在所有大鼠组的颗粒部分中相当。总之，盐依赖性高血压患者NOS 3亚细胞分布改变，可能与高血压和内皮功能障碍的发展有关。
A high-salt (HS) diet and angiotensin II (Ang II) are both associated with the development of hypertension and impaired endothelial function. We hypothesize that alterations in nitric oxide synthase (NOS) activity or subcellular localization of NOS 3 protein may contribute to endothelial dysfunction in salt-dependent hypertension. To test this hypothesis, two models of salt-dependent hypertension were studied: DOCA-salt and Ang II. For Ang II hypertension, rats were divided into 4 groups: control on normal or HS diet, Ang II-infused on normal or HS diet. The mesenteric arterial bed was isolated and frozen in liquid nitrogen. Frozen arteries were homogenized and separated into cytosolic and particulate fractions. NOS activity was assayed by determining the conversion of H-3-arginine to H-3-citrulline in the absence and presence of the NOS inhibitor, Nomega-nitro-L-arginine. NOS 3 protein expression was significantly increased in the cytosol of arteries from DOCA-salt compared with placebo rats and in Ang II-infused and Ang HS rats compared with control. NOS 3 expression in the particulate fraction was comparable among all groups. NOS activity (pmol/30 min/total protein) was significantly increased in the cytosolic fraction of arteries from DOCA-salt rats compared with placebo and in Ang HS rats compared with control. NOS activity was comparable in the particulate fraction in all rat groups. In conclusion, there is an altered subcellular distribution of NOS 3 in salt-dependent hypertension that may contribute to the development of hypertension and endothelial dysfunction.