Diminished Reserve for Cerebral Vasomotor Response to L-Arginine in the Elderly: Evaluation by Transcranial Doppler Sonography

BACKGROUND: Nitric oxide is pivotal in endothelially dependent vasodilatory regulation. An association of endothelial dysfunction with aging has been documented in the forearm and coronary vascular beds. However, the influence of aging in the human cerebral circulation, where regulation is particularly complex, is incompletely understood. OBJECTIVE: We systematically administered L-arginine, a precursor of nitric oxide, to evaluate the influence of aging on nitric oxide-mediated cerebral vasomotor regulation. METHODS: Among healthy volunteers, 20 older subjects (10 men, 10 women; age: 70.2 +/- 2.8 years) and 22 younger subjects (10 men, 12 women; age: 28.8 +/- 1.9 years) received intravenous infusions of L-arginine monochloride (500 mg/kg) over 30 min. Hemodynamic parameters were monitored continuously during and after infusion. The cerebral vasomotor response was estimated by transcranial Doppler sonography of the right middle cerebral artery. RESULTS: Infusion of saline as a control brought little change in the mean blood pressure, heart rate or cerebral blood flow velocity in either group. On administration of L-arginine, cerebral blood flow velocity increased and mean blood pressure decreased. After completion of infusion, both parameters rapidly normalized. While reduction of mean blood pressure did not differ between older and younger groups, the cerebral circulation in the older group showed a blunted, smaller, and more easily saturated vasomotor response compared to the younger group, though both groups had similar baseline values. CONCLUSION: Our results indicate a diminished nitric oxide-mediated cerebral vasomotor response in aging subjects. Additionally, transcranial Doppler sonography can be used to reliably evaluate age-related changes in the physiologic responses of the human cerebral circulation.