We examined the effect of aluminum on the permeability of the blood-brain barrier (BBB) during nitric oxide-blockade-induced chronic hypertension in rats. Animals were given the inhibitor of nitric oxide synthase, L-NAME (N-omega-nitro-L-arginine methyl ester), for 4 wk to induce chronic hypertension. Two groups of rats were given an intraperitoneal injection of aluminum chloride. The integrity of the BBB was assessed by a quantitative measurement for Evans blue (EB) dye. The arterial blood pressure in L-NAME- and L-NAME plus aluminum-treated animals was significantly elevated from 115+/-2.8 and 110+/-1.7 mm Hg to 174+/-5.2 and 175+/-4.8 mm Hg, respectively (p < 0.01). The EB dye content in the brain regions of the rats in the L-NAME group was increased, but there was no statistical significance compared to the saline group. The extravasation of EB dye was significantly increased in the brain regions of the animals treated with aluminum compared to the rats treated with saline (p < 0.05). A significantly higher EB dye content in the brain regions was observed in the L-NAME plus aluminum group compared to L-NAME, aluminum, and saline groups (p < 0.01). These findings indicate that exposure to a high level of aluminum leads to an additional increase in BBB permeability where nitric oxide-blockade-induced chronic hypertension potentiates the effect of aluminum to enhance BBB permeability to EB dye.