Role of coupling factor 6 in the pathogenesis of cardiovascular disease

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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