Effect of Perindopril on Cerebral Vasomotor Reactivity in Patients With Lacunar Infarction

Abstract

Background and Purpose-There is growing evidence that pharmacologic interference with the renin-angiotensin system may reduce risk of stroke, although the mechanism is unclear. Impaired reactivity of cerebral vessels has recently been recognized as a risk factor for stroke. We examined the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to acetazolamide in patients with lacunar cerebral infarction. Methods-We studied a cohort of male patients between 3 and 12 months after lacunar infarction confirmed on computed tomography. Each patient received perindopril 4 mg daily or matching placebo for 2 weeks in a randomized, double-blind, placebo-controlled crossover fashion. A 1-week washout period was observed between dosing periods. Cerebral vasomotor reactivity (increase in middle cerebral artery mean flow velocity in response to intravenous injection of 15 mg/kg acetazolamide) was measured before and after each dosing period using standard Doppler ultrasound techniques. Results-Twelve patients (mean age 63.2Ϯ2.3 years) completed the protocol. There was no treatment order effect.Cerebral vasomotor reactivity was significantly greater after perindopril treatment (percent change from baseline ϩ18.8Ϯ10.1% after perindopril, Ϫ4.6Ϯ4.1% after placebo; Pϭ0.032). Dosing with perindopril did not affect resting cerebral blood flow velocity (percent change from baseline ϩ3.1Ϯ9.5% after perindopril, Ϫ0.6Ϯ5.4% after placebo), nor was there a change in resting blood pressure (ϩ1.8 mm HgϮ3.1 after perindopril, ϩ1.4 mm HgϮ2.5 after placebo). Conclusions-This study provides evidence of a significant improvement in cerebral vasomotor reactivity induced by perindopril, beyond any effect on blood pressure. The results suggest a possible mechanism for the beneficial effect of ACE inhibition on stroke risk observed in recent clinical trials, and suggest a role for the renin-angiotensin axis in the pathophysiology of subcortical small vessel disease.

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