[Nitric oxide availability in cerebral microangiopathy].

OBJECTIVE

To develop a test of individual nitric oxide (NO) availability based on changes in erythrocyte rheological properties after incubation with a NO donor and to evaluate the role of these disorders in brain damage and development of cognitive impairment (CI) in cerebral small vessel disease (cSVD).

MATERIAL AND METHODS

In 73 cSVD patients (48 (65.8%) women, mean age 60.1±6.5), the rheological properties of erythrocytes before and after incubation with 10 μmol/L L-arginine-NO donor were evaluated using a laser-optical rotating cell analyzer, and the blood-brain barrier (BBB) permeability by MRI-T1 dynamic contrast.

RESULTS

Among the studied parameters of erythrocyte rheological properties, the best characteristic by ROC analysis was the rate of erythrocyte disaggregation (y-dis) after incubation with L-arginine (area under the curve 0.733 (0.609-0.856), sensitivity 67%, specificity 79%). Patients with a y-dis threshold >113 sec had more severe CI, arterial hypertension, white matter lesions, and increased BBB permeability in gray matter and normal-appearing white matter.

CONCLUSION

The prolonged rate of erythrocyte disaggregation in cSVD patients after incubation with L-arginine indicates the risk for disease progression due to decreased NO bioavailability/disruption of the functional L-arginine-eNOS-NO system. This test can be used to assess individual NO bioavailability and potentially identify indications for modifying therapy with NO donors such as L-arginine. Clinical trials are needed to standardize and evaluate the efficacy of NO donor therapy in patients with cSVD and CI.