In the present study, we examined the effects of chronic L-arginine treatment on plasma insulin levels and systolic blood pressure (SBP) in fructose-fed (F) rats. Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when compared with that in controls (plasma insulin, 311.3 +/- 11.4 v control 164.4 +/- 11.8 pmol/L, P < .05; SBP, 135.4 +/- 4.2 v control 105.5 +/- 1.3 mm Hg, P < .05). L-arginine treatment of fructose-hypertensive rats prevented the development of hyperinsulinemia and hypertension (plasma insulin, 200.1 +/- 7.5 pmol/L; P < .05 compared with that in F rats; SBP, 108.0 +/- 0.9 mm Hg; P < .05 compared with F rats). However, treatment with L-arginine did not influence any of these parameters in control rats. Statistical analysis of the data of plasma insulin level and SBP, revealed a significant correlation between these two variables. On the other hand, L-arginine treatment of F rats prevented the increased glucose and insulin concentrations in response to oral glucose challenge. L-arginine treatment also prevented the decrease in insulin sensitivity of F rats. These results indicate that L-arginine treatment is able to prevent fructose-induced hypertension and hyperinsulinemia. Our data also suggest a strong relationship between hyperinsulinemia and hypertension in this hypertensive rat model. Therefore, the antihypertensive effect Of L-arginine could be, at least in part, the result of the restoration of plasma insulin levels by its vasodilator ability to increase blood flow to insulin sensitive tissues. (C) 2002 American Journal of Hypertension, Ltd.