pCO(2) and pH regulation of cerebral blood flow

Abstract

CO(2) serves as one of the fundamental regulators of cerebral blood flow (CBF). It is widely considered that this regulation occurs through pCO(2)-driven changes in pH of the cerebral spinal fluid (CSF), with elevated and lowered pH causing direct relaxation and contraction of the smooth muscle, respectively. However, some findings also suggest that pCO(2) acts independently of and/or in conjunction with altered pH. This action may be due to a direct effect of CSF pCO(2) on the smooth muscle as well as on the endothelium, nerves, and astrocytes. Findings may also point to an action of arterial pCO(2) on the endothelium to regulate smooth muscle contractility. Thus, the effects of pH and pCO(2) may be influenced by the absence/presence of different cell types in the various experimental preparations. Results may also be influenced by experimental parameters including myogenic tone as well as solutions containing significantly altered HCO(3) (-) concentrations, i.e., solutions routinely employed to differentiate the effects of pH from pCO(2). In sum, it appears that pCO(2), independently and in conjunction with pH, may regulate CBF.

Keywords: carbon dioxide; cerebral blood flow; nitric oxide; respiratory acidification; respiratory alkalinization; vasoactive factors.

Figure 1

Effects of respiratory hypocapnia in the presence and absence of superfusate and of NO synthase inhibitor on blood flow velocity in rat ventral midbrain. Respiratory rate and/or tidal volume were increased in cranial window preparations superfused with Krebs-Ringer bicarbonate solution (−Dura) or in preparations with a burr hole in the cranium (+Dura). Laser-Doppler flow (flow velocity) was calculated as percent baseline (top panel). Arterial blood gas parameters and mean arterial pressure (MAP) are indicated in the lower panels and were similar in preparations with and without dura. Additional superfused preparations were exposed to 0.1 mM L-NNA for 30 min prior to respiratory hypocapnic challenge.

Figure 2

Potential cellular sites of action and vasoactive factor involvement in respiratory hypercapnia/hypocapnia-mediated relaxation/contraction. The effects of respiratory hypercapnia/hypocapnia may be mediated through accompanying changes in pH and/or directly by pCO₂. pH and/or pCO₂ act on the smooth muscle as well as on the endothelium, nerves, and astrocytes. These latter cell types release vasoactive factors, including PGI₂, H₂S, NO, endothelium-derived hyperpolarizing factor (EDHF), and endothelin-1 (ET-1).