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

Abstract

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.

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…On intravenous infusion of L-arginine, cerebral blood flow velocity increased and mean blood pressure decreased in healthy volunteers; however, the hypotensive effect did not differ between older (average age 70.2 years) and younger (28.8 years) groups. The cerebral circulation in the older group showed a blunted, smaller, and more easily saturated vasomotor response compared with that in the younger group (Okamoto et al, 2001). NO may be involved in the increased cerebral blood flow velocity.…”

Improved Cerebral Vasomotor Reactivity After Exercise Training in Hemiparetic Stroke Survivors

“…Diminished cVMR is reported in normal aging 3,6,23 and in individuals with a variety of vascular-related disease conditions. 24 -28 It exhibits diurnal variations, reaching low points during morning hours when stroke events are most prevalent.…”

Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1–Dependent Uncoupling of Endothelial Nitric Oxide Synthase

“…47,48 Although these observations would seem to suggest l-arginine supplementation as a therapeutic strategy, several studies have shown that l-arginine reactivity varies depending on time point after injury, vascular bed, and species studied, age, and the underlying disease. [48][49][50][51][52][53] One of the limitations of our study is that we focused on a specific time point after injury. Additional studies are needed to address the longitudinal course of vascular responses including earlier times after TBI and later time points after clinical recovery.…”