Effects of hypertension and antihypertensive treatments on sulfatide levels in serum and its metabolism.

Serum sulfatides are critical glycosphingolipids present in lipoproteins that work as modulators of thrombosis and hemostasis. Decreased serum sulfatide levels are suggested by our previous work to be related to cardiovascular disease (CVD). Hypertension, known to be an important risk factor for CVD, may affect serum sulfatide levels. However, how hypertension affects serum sulfatides directly and mechanistically is unknown. To elucidate these possible mechanisms, we investigated changes in serum sulfatide levels and their metabolism using an established experimental model of hypertension that uses continuous infusion of angiotensin II (AngII) into mice. Furthermore, we also examined the effects of four different antihypertensive drugs (losartan, irbesartan, nifedipine, and hydralazine) on serum sulfatide metabolism. Serum levels of sulfatides were found to be decreased in groups in which only hypertension was induced (AngII only), whereas they were increased in groups with reduced blood pressure (antihypertensives only) and ameliorated to increasingly normal levels in groups with induced hypertension that were also treated (AngII+antihypertensives). Changes in serum sulfatides were strongly related to hepatic expression levels of cerebroside sulfotransferase (CST), which is a key enzyme involved in sulfatide synthesis. Furthermore, the current study suggests that the primary factors affecting CST expression are oxidative stress, peroxisome proliferator-activated receptor α activity and blood pressure itself. This study demonstrates that hypertension significantly decreases levels of serum sulfatides by reducing hepatic CST expression via various effects mediated by AngII. Antihypertensive treatments can ameliorate abnormalities in serum sulfatide levels and may partially prevent hypertension related CVD by positively affecting sulfatide metabolism.