Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia.

Enrasentan is an antagonist of endothelin (ET) receptors. Previous studies have shown that antagonism of ET receptors might represent a new approach to the treatment of hypertension. Rats with a high-fructose diet (HFD) develop hyperinsulinemia, hypertriglyceridemia, and hypertension; renal and cardiac damage. The aim of this study was to evaluate whether enrasentan could reverse the hypertension and reduce the target organ damage induced by an HFD. Fifty-five WKY rats were divided into 6 groups; 35 animals received HFD for a month; thereafter 5 animals were killed, and the others were treated either with enrasentan (n = 10), hydralazine (n = 10), or placebo (n = 10) for a further month while on the HFD. Twenty animals were kept on a standard diet throughout the study; either placebo (n = 10) or enrasentan (n = 10) was administered during the second month. Enrasentan and hydralazine completely eliminated the HFD-induced increase in blood pressure; however, only enrasentan reduced the renal and cardiac damage caused by the diet. In conclusion, enrasentan was effective both in normalizing blood pressure and in reducing renal and cardiac damage; the organ protection cannot be attributed solely to the antihypertensive effect, because it was absent in the case of hydralazine, despite successful control of blood pressure.