Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction

Abstract

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO₂-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco₂, CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO₂ vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO₂ inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 ± 75 vs. 297 ± 31%; P = 0.01, AUC ΔFBF: 173 ± 17 vs. 127 ± 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO₂ vasoreactivity was impaired in patients compared with controls: 1.19 ± 0.1 vs. 1.54 ± 0.1 cm·s⁻¹·mmHg⁻¹; P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO₂ vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO₂-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.