Alterations in arterial CO2 rather than pH affect the kinetics of neurovascular coupling in humans.

Abstract

We investigated the influence of arterial ( ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso-oxic alterations in prior to and following intravenous NaHCO3 to acutely elevate arterial pH and [HCO3- ]. The NVC response was not altered following NaHCO3 between stepwise stages; therefore, NVC is acutely mediated by rather than the prevailing arterial [H+ ]/pH. The NVC response was attenuated by 27-38% with -10mmHg and the absolute peak change was reduced by -19% with +10mmHg irrespective of acutely elevated arterial pH/[HCO3- ]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24±5 vs. 7±5s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness. Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre-clinical work indicates that arterial ( ) mediates NVC independently of arterial/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus-evoked NVC test during matched stepwise iso-oxic alterations in (hypocapnia: -5, -10mmHg; hypercapnia: +5, +10mmHg) prior to and following intravenous NaHCO3 (8.4%, 50mEq/50ml) that elevated arterial pH (7.406±0.019 vs. 7.457±0.029; P<0.001) and [HCO3- ] (26.2±1.5 vs. 29.3±0.9mEq/l; P<0.001). Although the NVC response was collectively attenuated by 27-38% with -10mmHg (stage post hoc: all P<0.05), this response was unaltered following NaHCO3 (all P>0.05) irrespective of the higher pH (P=0.002) at each matched stage of (P=0.417). The absolute peak change was reduced by -19 ±41% with +10mmHg irrespective of acutely elevated arterial pH/[HCO3- ] (stage post hoc: P=0.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24±5 vs. 7±5s, respectively; stage effect: P<0.001). Overall, these findings indicate that temporal patterns in NVC are acutely regulated by rather than arterial pH per se in the setting of acute metabolic alkalosis in humans.