Role of coupling factor 6 in the pathogenesis of cardiovascular disease

血压的盐敏感性是心血管事件的重要危险因素。偶联因子6是前列环素合成的内源性抑制因子和血管紧张剂。为探讨偶联因子6在高血压患者盐敏感性中的作用，对30例高血压病患者分别给予正常盐饮食(12g盐/d)3d、低盐饮食(2g盐)7d和高盐饮食(20~23g盐)7d。血压正常的对照组(n=27)接受正常和低盐饮食。用放射免疫法测定正常盐饮食条件下EH患者血浆偶联因子6水平(17.6±1.7vs12.8±0.5 ng/ml，p&lt；0.01)。而正常人限盐后血浆偶联因子6水平无明显变化，EH患者限盐后血浆偶联因子6水平降低，盐负荷后血浆偶联因子6水平升高。限盐和负荷后血浆偶联因子6水平的百分比变化与平均血压呈正相关(r=0.57，p&lt；0.01)。在高盐饮食中，口服抗坏血酸可引起血浆偶联因子6和8-表前列腺素F_2和8-表前列腺素F_2水平下降，但不影响血压水平。血浆偶联因子6水平与一氧化氮水平变化百分率呈负相关(r=0.51，p&lt；0.05)。这些表明，循环偶联因子6在人类高血压中受盐摄入量的调节，可能是通过活性氧，它可能与盐敏感性心血管疾病的高风险有关。

Salt sensitivity of blood presure ins an important risk factor for cardiovascular events. Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis and a vasoonstrictor. We investigated the role of coupling facor 6 in salt sensitivity in human hypentension.The patients with essential hypertension (EH)(n=30) received a series of normal salt diet (12g salt/day) for 3 days, low salt diet (2g salt) for 7 days, and high salt diet (20-23g salt) for 7 days. Normotensive control subjects (n=27) received normal and low salt diets. The plasma level of coupling factor 6, measured by radioimmunoassay, during normal salt diet was higher in patients with Eh than in normotensive subjects (17.6±1.7 vs 12.8±0.5 ng/ml, p<0.01). Whereas the plasma level of coupling factor 6 was unchanged after salt restriction in normotensive subjects , it was decreased after salt restriction and increased after salt loading inpatients with EH. The percent changes in plasma coupling factor 6 level after salt restriction and loading were positively correlated with those in mean blood pressure (r=0.57, p<0.01). During high salt diet, oral administration of ascorbic acid induced the decrease in plasma levels of coupling factor 6 and 8-epi-prostaglandin F_<2xx> without affecting blood pressure level. The percent changes in plasma coupling factor 6 level were negatively correlated with those in plasma nitric oxide level (r=0.51, p<0.05). These indicate that circulating coupling factor 6 is modulated by salt intake in human hypertension presumably via reactive oxygen species and it may be involved in higher cardiovascular risk in salt sensitivity