Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar infarction.
OBJECTIVE
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.
Walters
Matthew
M
Gardiner Institute, Western Infirmary, Division of Cardiovascular and Medical Sciences, University Department of Medicine and Therapeutics, University of Glasgow, Glasgow, Scotland. m.walters@clinmed.gla.ac.uk
Muir
Scott
S
Shah
Imtiaz
I
Lees
Kennedy
K
D000086:Acetazolamide / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D020520:Brain Infarction / Q000188:drug therapy* / Q000503:physiopathology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use*; D017585:Ultrasonography, Doppler, Transcranial
D000806:Angiotensin-Converting Enzyme Inhibitors; D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide; D020913:Perindopril