PERINDOPRIL TREATMENT IN THE PREVENTION OF STROKE IN EXPERIMENTAL-ANIMALS

Objective To determine the effect of perindopril treatment and treatme nt withdrawal in the prevention of stroke in male stroke-prone spontan eously hypertensive rats (SPSHR). Design After weaning at 4 weeks of a ge, male SPSHR were given a Japanese-style rat diet which induces stro ke in these animals. Beginning at 6 weeks of age, SPSHR were treated w ith either distilled water (control) or different daily dosages of per indopril (1 or 4 mg/kg) by gavage for 24 weeks followed by treatment w ithdrawl. Additional subgroups were treated with the 4 mg/kg dose for different durations (8, 12 or 24 weeks) before treatment withdrawal. T reatment effects on blood pressure, heart rate and body weight were st udied during the treatment period and after the withdrawal of the trea tment. Myogenic and mechanical properties of the middle cerebral arter ies were studied in control SPSHR that had developed stroke, in treate d SPSHR at the end of the treatment period, and at certain intervals a fter the withdrawal of the treatment. Methods Systolic blood pressure, heart rate and body weight of control and treated SPSHR were determin ed at regular intervals before, during and after the treatment withdra wal periods until they died from stroke, or until 42 or 43 weeks of ag e when the study was terminated. Functional studies of the cerebral ar teries were carried out using a pressurized artery system. At necropsy , macroscopic and microscopic examinations were made of the kidneys an d brain. Results Untreated SPSHR usually died of stroke-related compli cations by 14 weeks of age. The middle cerebral arteries from these an imals had lost their ability to contract in response to pressure incre ase. Chronic treatment of SPSHR with perindopril when initiated at 6 w eeks of age attenuated the sharp blood pressure rise, and prevented th e development of stroke during the treatment period. This was associat ed with the preservation of the myogenic response of the middle cerebr al arteries to pressure increase, and the prevention of tissue damage in the kidneys and brain. After withdrawl of the treatment, SPSHR trea ted for a longer period (12 or 24 weeks) also survived longer than tho se treated for a shorter period (8 weeks). The subsequent loss of myog enic response in the middle cerebral arteries was associated with the development of stroke and death in these treatment withdrawl groups. C onclusion Chronic treatment with perindopril is beneficial for the pre vention of stroke in SPSHR, through the preservation of the myogenic r esponse properties of the cerebral arteries, and the attenuation of ti ssue damage in the brain and kidneys.