EFFECTS OF LOSARTAN ON BLOOD-PRESSURE, METABOLIC ALTERATIONS, AND VASCULAR REACTIVITY IN THE FRUCTOSE-INDUCED HYPERTENSIVE RAT

Fructose feeding induces a moderate increase in blood pressure levels in normal rats that is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore the mechanisms underlying fructose-induced hypertension, the effects of the AT(1) receptor antagonist losartan on blood pressure, insulin resistance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch (control), and half of each group received losartan (1 mg/kg per day) in the drinking water. Fructose-fed rats showed higher (P<.05) blood pressure levels and plasma concentrations of triglycerides and insulin than those of controls. Losartan treatment prevented both blood pressure elevation and hyper-insulinemia in fructose-fed rats but not elevation of plasma triglycerides. Plasma glucose and insulin levels in response to an oral glucose load were higher (P<.05) in fructose-fed rats than in controls. These exaggerated responses were prevented by losartan treatment. No differences in the constrictor responses of mesenteric vascular beds to KCl (60 mu mol), angiotensin II (1 nmol), phenylephrine (10(-5) mol/L), or endothelin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontracted mesenteric vascular beds and constrictor to response to the nitric oxide synthesis inhibitor N-G-nitro-L-arginine methyl ester (100 nmol) were comparable in both groups. Losartan blunted angiotensin II constriction and reduced (P<.05) responses to phenylephrine in all groups. In conclusion, these results suggest that angiotensin II plays an important role in the blood pressure elevation and in the insulin resistance induced by fructose feeding in rats. The mechanisms underlying these effects appear to be dependent on neither a vascular hyperreactivity to constrictor factors nor an endothelial dysfunction related to a decreased production of nitric oxide.