高同型半胱氨酸血症对孕鼠动脉血压和一氧化氮生成的影响。
Effects of hyperhomocysteinemia on arterial pressure and nitric oxide production in pregnant rats.
机构信息
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
出版信息
Am J Hypertens. 2009 Oct;22(10):1115-9. doi: 10.1038/ajh.2009.130. Epub 2009 Jul 23.
BACKGROUND
An elevated plasma level of homocysteine (hyperhomocysteinemia) is thought to be an important risk factor for a variety of cardiovascular diseases including preeclampsia. Although clinical studies have reported a two- to threefold elevation in plasma levels of homocysteine in women who developed preeclampsia, the importance of hyperhomocysteinemia in causing endothelial dysfunction and increases in arterial pressure during pregnancy is unknown.
METHODS
Therefore, the purpose of this study was to determine the effects of a two- to threefold elevation in plasma homocysteine levels on arterial pressure, chronic pressure-natriuresis relationship, and endothelial factors during pregnancy in the rat. Homocysteine treatment for 4 weeks increased plasma homocysteine levels in pregnant rats from 7.1 +/- 1.9 to 16.7 +/- 2.3 micromol/l.
RESULTS
Homocysteine treatment decreased urinary nitrate/nitrite levels from 53 +/- 7 vs. 39 +/- 5 (micromol/24 h/kg body weight) in pregnant rats whereas having no effect on urinary excretion of endothelin. Homocysteine treatment had no effect on mean arterial pressure (MAP) in pregnant rats (104 +/- 2 vs. 107 +/- 3 mm Hg) nor on the chronic pressure-natriuresis relationship.
CONCLUSIONS
These results suggest that although hyperhomocysteinemia decreases nitric oxide (NO) production in pregnant rats, hyperhomocysteinemia does not affect MAP, the chronic pressure-natriuresis relationship, or urinary excretion of endothelin in pregnant rats. Moreover, the reported two- to threefold elevation in plasma level of homocysteine in women with preeclampsia is unlikely to contribute to the hypertension of preeclampsia.
背景
同型半胱氨酸（高同型半胱氨酸血症）水平升高被认为是多种心血管疾病的重要危险因素，包括先兆子痫。虽然临床研究报告称，先兆子痫患者血浆同型半胱氨酸水平升高 2 至 3 倍，但高同型半胱氨酸血症在怀孕期间导致内皮功能障碍和动脉压升高的重要性尚不清楚。
方法
因此，本研究旨在确定血浆同型半胱氨酸水平升高 2 至 3 倍对怀孕大鼠动脉压、慢性压力-利钠关系和内皮因子的影响。同型半胱氨酸处理 4 周使怀孕大鼠的血浆同型半胱氨酸水平从 7.1 ± 1.9 增加到 16.7 ± 2.3μmol/L。
结果
同型半胱氨酸处理使怀孕大鼠的尿硝酸盐/亚硝酸盐水平从 53 ± 7 降至 39 ± 5（μmol/24 h/kg 体重），而对内皮素的尿排泄无影响。同型半胱氨酸处理对怀孕大鼠的平均动脉压（MAP）（104 ± 2 对 107 ± 3 mmHg）或慢性压力-利钠关系均无影响。
结论
这些结果表明，尽管高同型半胱氨酸血症降低了怀孕大鼠的一氧化氮（NO）生成，但高同型半胱氨酸血症不影响 MAP、慢性压力-利钠关系或怀孕大鼠的内皮素尿排泄。此外，报道的先兆子痫妇女血浆同型半胱氨酸水平升高 2 至 3 倍不太可能导致先兆子痫的高血压。
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