Bosentan reduces blood pressure and the target-organ damage induced by a high-fructose diet in rats

Background Rats fed a high-fructose diet develop hyperinsulinaemia, hypertr iglyceridaemia, hypertension, renal changer similar to those in diabetic ra ts and left ventricular hypertrophy with deposition of collagen. Bosentan i s an antagonist of endothelin receptors, Other authors have demonstrated th at bosentan is effective in preventing the increase in blood pressure induc ed by a high-fructose diet but, until now, the effect of the drug on the ta rget organs has not been investigated. Objective To evaluate whether bosentan is effective, not only in reducing b lood pressure, but also in limiting the renal and cardiac changes induced b y a high-fructose diet. Methods Forty Wistar-Kyoto (WKY) male rats were divided into four groups: g roups 1 and 2 received a high-fructose diet, groups 3 and 4 received a stan dard diet for 1 month. Thereafter, the following treatments were administer ed: group 1, high-fructose diet plus bosentan 100 mg/kg per day; group 2, h igh-fructose diet plus placebo; group 3, standard diet plus bosentan 100 mg /kg per day; group 4, standard diet plus placebo. After a further 1 month, all animals were killed. A morphometric analysis was performed by examining 100 glomeruli for each animal. Renal deposits of collagen and fibronectin and cardiac deposits of collagen III were measured by means of immunochemis try. Results By the end of the study, bosentan had completely reversed the incre ase in blood pressure induced by a high-fructose diet, without modifying th e blood pressure in normotensive rats. Moreover, bosentan reduced glomerula r hypertrophy and deposits of collagen and fibronectin in the kidney and ca rdiac deposits of collagen III. Conclusions The results of this study demonstrate that bosentan not only no rmalizes blood pressure, but also protects target organs in rats receiving a high-fructose diet. J Hypertens 1999, 17:1843-1848 (C) Lippincott William s & Wilkins.