The authors investigated the vasorelaxant properties of the aqueous (Aq-EF) and acid n-butanolic (acn-BuOH) extractable fractions from Ilex paraguariensis leaves. Perfusion pressure was evaluated using isolated and perfused mesenteric arterial beds (MABs) from rats fed hypercholesterolemic and standard diets. Extract-induced vasorelaxation in the presence and absence of various inhibitors was examined following precontraction of the MABs with methoxamine (30 microM) solution. In hypercholesterolemic-diet rats, relaxation in intact MABs was significantly decreased with ac-n-BuOH-EF bolus (300, 600, 900 microg) in comparison to those in standard-diet rats. After the endothelium was stripped from the MABs, the vascular responses to ac-n-BuOH-EF and 900 microg bolus of Aq-EF were significantly changed. Treatment of the MABs with an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methylester hydrochloride (L-NAME, 10 mM), did not change either ac-n-BuOH-EF- or Aq-EF-induced vasodilation except for the 900 microg bolus of Aq-EF. The guanilate cyclase inhibitor methylene blue (100 microM) did not affect vasodilation for either fraction in the MABs from the hypercholesterolemic-diet rats. The chronic oral administration of I. paraguariensis extract in hypercholesterolemic-diet rats resulted in a significant reduction in serum levels of cholesterol and triglycerides. These results suggest that I. paraguariensis ac-n-BuOH-EF and Aq-EF induce vasodilation in standard-diet rats in a dose-dependent manner and that the hypercholesterolemic diet substantially reduced the effect of ac-n-BuOH-EF on precontracted MABs.