The importance of aldosterone suppression in the restoration of cerebrovascular myogenic function in SHRsp during post stroke Captopril and Losartan treatment

Abstract

Treatment of Kyoto Wistar stroke prone spontaneously hypertensive rats (SHRsp) with Captopril (CAP) or Losartan (LOS) after hemorrhagic stroke (HS) restores pressure dependent constriction (PDC) in middle cerebral arteries (MCAs) . We assessed the importance of aldosterone (ALD) suppression during both treatments. Plasma ALD was elevated in SHRsp with HS over prestroke levels (3.9 ± 0.8 nM vs 0.15 ± 0.09 nM). SHRsp with HS were treated orally with 50mg/kg/day CAP or 35 mg/kg/day LOS for 28 days. During the last 10 days of treatment ALD (0.66 μg/hr) or vehicle was infused via an osmotic pump . CAP and LOS treatment suppressed plasma ALD (0.23 ± 0.07 and 0.075 ± 0.044 nM respectively), whereas supplementation elevated ALD (6.27±1.75 and 4.49 ± 0.80 nM respectively). ALD supplementation did not alter BP. After 28 days of CAP or LOS treatment, MCAs from SHRsp with HS (studied using a pressure myograph) regained PDC and the ability to constrict in response to protein kinase C activation (1μM phorbol dibutyrate) and elevated [K+]o depolarization. ALD supplementation prevented these changes in CAP but not LOS treated SHRsp. Elevation in plasma ALD enhance the deterioration of myogenic function. We believe that poststroke treatment with LOS (vs CAP) promotes systemic beneficial effects that permit the restoration of cerebrovascular function even under conditions of where plasma ALD is elevated.