Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar infarction

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 63.2 +/- 2.3 years) completed the protocol. There was no treatment order effect. Cerebral vasomotor reactivity was significantly greater after perindopril treatment ( percent change from baseline + 18.8 +/- 10.1% after perindopril, -4.6 +/- 4.1% after placebo; P = 0.032). Dosing with perindopril did not affect resting cerebral blood flow velocity (percent change from baseline + 3.1 +/- 9.5% after perindopril, -0.6 +/- 5.4% after placebo), nor was there a change in resting blood pressure (+ 1.8 mm Hg +/- 3.1 after perindopril, + 1.4 mm Hg +/- 2.5 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.