Beraprost sodium is a stable analog of the vasodilator, platelet antiaggregatory eicosanoid, prostacyclin. Experiments were performed to determine whether long-term therapy with beraprost produces vascular protective effects in saline-drinking stroke-prone spontaneously hypertensive rats (SHRSPs). Oral beraprost at 30, 100, or 300 micrograms/kg/day starting at 8.4 weeks of age did not affect the progressive increase of systolic blood pressure (measured by tail-cuff plethysmography) in these rats. Additional experiments in SHRSPs, prepared for continuous monitoring of blood pressure by radiotelemetry, revealed that oral beraprost administration reduced mean arterial pressure but that these hypotensive responses were not sustained (< 4 h). In all SHRSPs receiving oral beraprost, proteinuria and cerebrovascular lesions developed. In contrast, continuous subcutaneous infusion of beraprost at 2.8 mg/kg/day from age 8.3-12.3 weeks reduced systolic blood pressure and markedly diminished the development of renal lesions and the occurrence of stroke in saline-drinking SHRSPs. Beraprost at 0.9 mg/kg/day reduced blood pressure less than did 2.8 mg/kg/day and provided partial protection against cerebral and renal lesions after a 4-week infusion period. These results indicate that long-term subcutaneous infusion of beraprost can protect saline-drinking SHRSPs against stroke and renal damage. This effect is not readily dissociated from the ability of beraprost to reduce blood pressure in SHRSPs.