BENEFICIAL ACTION OF BERAPROST SODIUM, A PROSTACYCLIN ANALOG, IN STROKE-PRONE RATS

Beraprost sodium is a stable analog of the vasodilator, platelet antia ggregatory eicosanoid, prostacyclin. Experiments were performed to det ermine whether long-term therapy with beraprost produces vascular prot ective effects in saline-drinking stroke-prone spontaneously hypertens ive rats (SHRSPs). Oral beraprost at 30, 100, or 300 mu g/kg/day start ing at 8.4 weeks of age did not affect the progressive increase of sys tolic blood pressure (measured by tail-cuff plethysmography) in these rats. Additional experiments in SHRSPs, prepared for continuous monito ring of blood pressure by radiotelemetry, revealed that oral beraprost administration reduced mean arterial pressure but that these hypotens ive responses were not sustained (<4 h). In all SHRSPs receiving oral beraprost, proteinuria and cerebrovascular lesions developed. In contr ast, continuous subcutaneous infusion of beraprost at 2.8 mg/kg/day fr om age 8.3-12.3 weeks reduced systolic blood pressure and markedly dim inished the development of renal lesions and the occurrence of stroke in saline-drinking SHRSPs. Beraprost at 0.9 mg/kg/day reduced blood pr essure less than did 2.8 mg/kg/day and provided partial protection aga inst 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 red uce blood pressure in SHRSPs.