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, hyperinsuli nemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore th e mechanisms underlying fructose-induced hypertension, the effects of the AT(1) receptor antagonist losartan on blood pressure, insulin resi stance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diet s containing 60% fructose or 60% starch (control), and half of each gr oup received losartan (1 mg/kg per day) in the drinking water. Fructos e-fed rats showed higher (P<.05) blood pressure levels and plasma conc entrations of triglycerides and insulin than those of controls. Losart an treatment prevented both blood pressure elevation and hyper-insulin emia in fructose-fed rats but not elevation of plasma triglycerides. P lasma glucose and insulin levels in response to an oral glucose load w ere higher (P<.05) in fructose-fed rats than in controls. These exagge rated responses were prevented by losartan treatment. No differences i n the constrictor responses of mesenteric vascular beds to KCl (60 mu mol), angiotensin II (1 nmol), phenylephrine (10(-5) mol/L), or endoth elin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontract ed 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 const riction and reduced (P<.05) responses to phenylephrine in all groups. In conclusion, these results suggest that angiotensin II plays an impo rtant role in the blood pressure elevation and in the insulin resistan ce induced by fructose feeding in rats. The mechanisms underlying thes e effects appear to be dependent on neither a vascular hyperreactivity to constrictor factors nor an endothelial dysfunction related to a de creased production of nitric oxide.