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, hypertriglyceridaemia, hypertension, renal changes similar to those in diabetic rats and left ventricular hypertrophy with deposition of collagen. Bosentan is an antagonist of endothelin receptors. Other authors have demonstrated that bosentan is effective in preventing the increase in blood pressure induced by a high-fructose diet but, until now, the effect of the drug on the target organs has not been investigated.


OBJECTIVE
To evaluate whether bosentan is effective, not only in reducing blood pressure, but also in limiting the renal and cardiac changes induced by a high-fructose diet


METHODS
Forty Wistar-Kyoto (WKY) male rats were divided into four groups: groups 1 and 2 received a high-fructose diet, groups 3 and 4 received a standard diet for 1 month. Thereafter, the following treatments were administered: group 1, high-fructose diet plus bosentan 100 mg/kg per day; group 2, high-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 immunochemistry.


RESULTS
By the end of the study, bosentan had completely reversed the increase in blood pressure induced by a high-fructose diet, without modifying the blood pressure in normotensive rats. Moreover, bosentan reduced glomerular hypertrophy and deposits of collagen and fibronectin in the kidney and cardiac deposits of collagen III.


CONCLUSIONS
The results of this study demonstrate that bosentan not only normalizes blood pressure, but also protects target organs in rats receiving a high-fructose diet.
Cosenzi
A
A
Istituto di Medicina Clinica University of Trieste, Italy.
Bernobich
E
E
Plazzotta
N
N
Seculin
P
P
Bellini
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013449:Sulfonamides / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004040:Dietary Carbohydrates; D013449:Sulfonamides; D005632:Fructose; D000077300:Bosentan