Abstract W P212: Combination Therapy With Amlodipine and Irbesartan Persists a Neuroprotective Effect Associated With Glial Deactivation on Paraventricular Nucleus in Hypertensive Rats

Although combination therapy with calcium channel antagonist and angiotensin II receptor blocker is sometimes more effective for hypertension than monotherapy, it is little known the significant roles against stroke onset. In this study, we investigated the beneficial effect of the combination therapy with amlodipine and irbesartan against stroke onset in stroke-prone spontaneously hypertensive rats (SHRSP). High-salt-loaded SHRSP were assigned to 1)vehicle, 2)amlodipine (AM; 2mg/kg/day), 3)irbesartan (IR; 20mg/kg/day), and 4)AM+IR. The drugs were given every day until 35 days. Incidences of neurological deficit and mortality were monitored every day and blood pressure was measured at 7 and 28 days. Cerebral blood flow (CBF), weight of brain and left ventricle (LV) and histological evaluations were conducted at 42 days. The blood pressure in AM and AM+IR groups were significantly reduced compared with that in vehicle groups. Although the incidence of neurological deficit and mortality until 28 days were 90% and 40% in vehicle group, the rats in treatment groups were almost healthy until 35 days. After the drugs discontinued, abnormal signs were frequently seen in monotherapy groups until 42 days (neurological deficit; AM 50%, IR 50%, AM+IR 0%, mortality; AM 30%, IR 10%, AM+IR 0%). Although there was no significant difference in CBF among the groups, the weight of brain and LV in AM+IR group were decreased compared with those in single treatment groups. Histological findings showed that glial activation at paraventricular nucleus and atrophy of white matter were more seen in stroke group compared with non-stroke groups. These data suggest that the therapy with AM+IR persist a neuroprotective effect against hypertension-induced stroke onset and the effect might associate with glial deactivation on paraventricular nucleus.