Disulfonic
stilbenes combine with the
carrier protein involved in
anion transport and inhibit the exchange of Cl- for HCO3- in a variety of biomembranes. Our aim was to determine whether such a mechanism is operative in the regulation of cerebrospinal fluid (CSF) [HCO3-] in metabolic
alkalosis. In anesthetized, curarized, and artificially ventilated dogs either mock CSF (group I, 9 dogs) or mock CSF containing
SITS, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic
acid (group II, 7 dogs) was periodically injected into both lateral cerebral ventricles. During 6 h of isocapnic metabolic
alkalosis, produced by
intravenous infusion of Na2CO3
solution, plasma [HCO3-] was increased by approximately 14 meq/l in both groups. In
SITS-treated animals the mean cisternal CSF [HCO3-] increased by 7.7 meq/l after 6 h, and this was significantly higher than the respective increment, 3.5 meq/l, noted in the control group. Increments in CSF [HCO3-] in both groups were reciprocated by decrements in CSF [Cl-] with CSF [Na+] remaining unchanged. Cisternal CSF PCO2 and
lactate concentrations showed similar increments in both groups. It is hypothesized that in metabolic
alkalosis a carrier transports HCO3- out of cerebral fluid in exchange for Cl- and that
SITS inhibits this mechanism. The efflux of HCO3- out of CSF in metabolic
alkalosis would minimize the rise in CSF [HCO3-] brought about by HCO3-] influx from blood into CSF and therefore contributes to the CSF [H+] homeostasis.