L-arginine-mediated vasoreactivity in patients with a risk of stroke.
OBJECTIVE
L-arginine is the substrate for nitric oxide (NO) production and has been shown to induce an endothelium-dependent increase in cerebral blood flow in humans. We studied the hypothesis that L-arginine-mediated vasoreactivity is impaired in patients with cardiovascular risk factors and a risk of stroke.


METHODS
55 patients with cardiovascular risk factors (mean age 63.0 +/- 8.5 years) were included in the study. 45 of them had a history of previous minor stroke or transient ischemic attack (TIA) while 10 patients had cardiovascular risk factors but no previous cerebral ischemic event. Endothelium-dependent changes in cerebral blood flow during the infusion of 30 g L-arginine were assessed by continuous transcranial Doppler sonography of both middle cerebral arteries, intima-media thickness (IMT) of the common carotid artery, by Duplex sonography. Associations between risk factors, IMT, L-arginine reactivity and previous cerebrovascular events were analyzed by stepwise multiple linear regression analysis and patient groups were compared.


RESULTS
Normal young volunteers showed an L-arginine-mediated increase in mean flow velocity of 22 +/- 8%; L-arginine reactivity of the 55 patients was 28 +/- 10%. Patients with a history of stroke or TIA had significantly higher flow velocity responses to L-arginine (29 +/- 10%) than patients with cardiovascular risk factors but no previous cerebrovascular event (21 +/- 8%, p < 0.05). Stepwise multiple linear regression analysis showed a significant association of enhanced L-arginine reactivity with previous stroke/TIA (p < 0.001) and elevated fibrinogen levels (p < 0.05) but not with age, IMT, hypertension, cholesterol or other risk factors. The same regression model showed an association between IMT and previous stroke/TIA (p < 0.001) and serum cholesterol levels (p < 0.05) but not L-arginine reactivity.


CONCLUSIONS
L-arginine reactivity of the cerebral vessels may be assessed by Doppler sonography and was enhanced in patients with a history of stroke or TIA. It was independent of IMT of the carotid arteries. We conclude that enhanced L-arginine reactivity is a potential marker for cerebral endothelial dysfunction and an independent indicator for an increased risk of stroke.
Zimmermann
Carolin
C
Department of Neurology, Krankenhaus München-Harlaching, München, Germany.
Wimmer
Martin
M
Haberl
Roman L
RL
D000368:Aged; D001120:Arginine / Q000008:administration & dosage; D001783:Blood Flow Velocity / Q000187:drug effects*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D020521:Stroke / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D017585:Ultrasonography, Doppler, Transcranial
D001120:Arginine