title: 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 CO(2)-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 Pco(2), 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. CO(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO(2) 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 DeltaFBF: 173 +/- 17 vs. 127 +/- 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO(2) 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 CO(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.
authors.affiliation: J. Recanati Autonomic Dysfunction Center, Medicine A, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel.
authors.forename: Shahar
authors.initials: S
authors.lastname: Lavi
authors.forename: Diana
authors.initials: D
authors.lastname: Gaitini
authors.forename: Victor
authors.initials: V
authors.lastname: Milloul
authors.forename: Giris
authors.initials: G
authors.lastname: Jacob
mesh_terms: D001921:Brain / Q000098:blood supply* / Q000502:physiology; D002245:Carbon Dioxide / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
chemical_list: D020030:Nitric Oxide Donors; D002245:Carbon Dioxide; D009599:Nitroprusside; D009569:Nitric Oxide