Impaired cerebral CO sub(2) vasoreactivity: association with endothelial dysfunction

• Published in: American Journal of Physiology: Cell Physiology 2006-10, Vol.291 (4), p.H1856-H1861
• Main Authors: Lavi, Shahar, Gaitini, Diana, Milloul, Victor, Jacob, Giris
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563

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 sub(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 sub(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 sub(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO sub(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 plus or minus 75 vs. 297 plus or minus 31%; P = 0.01, AUC Delta FBF: 173 plus or minus 17 vs. 127 plus or minus 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO sub(2) vasoreactivity was impaired in patients compared with controls: 1.19 plus or minus 0.1 vs. 1.54 plus or minus 0.1 cm.s super(-1).mmHg super(-1); P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO sub(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO sub(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.