4-acetamido-4--isothiocyanatostilbene-2-2--disulfonic-acid and Hypercapnia

In 11 anesthetized rats, we tested the hypothesis that carrier-mediated anion transport in part determines the medullary chemoreceptor response to acute hypercapnia by infusing the transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in mock cerebrospinal fluid (CSF) into the cisterna magna. In five additional rats with sham CSF infusion, we found no effect of mock CSF on the response to rebreathing CO2. Dye infused into the cistern stained the putative chemoreceptor areas on the ventral surface of the medulla. DIDS, at 10 to 1,000 nM, increased the respiratory response to CO2 in a dose-related manner but had no effect on arterial pressure or heart rate. At 1,000 nM, the hypercapnic minute ventilation response was almost doubled because of both volume and rate of breathing. We conclude that the net effect of anion transport is to mitigate the stimulus to the medullary chemoreceptors during acute hypercapnia.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Animals; Blood Pressure; Carbon Dioxide; Cerebrospinal Fluid; Heart Rate; Hypercapnia; Rats; Rats, Inbred Strains; Respiration; Stilbenes; Tidal Volume

The possibility that the increase in cerebrospinal fluid (CSF) [HCO-3] observed during respiratory acidosis could be the result of a decrease in CSF [Cl-] was studied by blocking a putative Cl--HCO-3 exchange transport system. Anesthetized dogs (pentobarbital 30 mg, iv) were given either 4,4'-diisothiocyano-2,2'-disulfonate stilbene (DIDS, 0.02 mumol/kg) or pyridoxal 5-phosphate (P-5-P, 4 mumol/kg) in the lateral cerebral ventricles and maintained either normocapnic (RA) or hypercapnic (5% CO2). CSF and arterial Pco2, pH, [Na+], [K+], [Ca2+], [Cl-], and [lactate] were determined. [HCO-3] was calculated. Samples were drawn before and 4 h after the drug was administered. In control dogs on RA no significant change was observed in any measured parameter after 4 h. Dogs receiving either DIDS or P-5-P and on RA had decreased CSF [Na+] of 2-4 meq/l and CSF [Cl-] of 6 meq/l. CSF [HCO-3] in DIDS dogs decreased approximately 5 meq/l. There was no significant change in CSF [HCO-3] in P dogs. After 4 h of 5% CO2, control dogs had decreased CSF [Cl-] of 3 meq/l and CSF [HCO-3] increased approximately 4 meq/l. Dogs receiving DIDS or P-5-P and breathing 5% CO2 for 4 h had decreased CSF [Cl-] of 6-9 meq/l and [HCO-3] increased of 7-9 meq/l. CSF [Na+] did not change during respiratory acidosis in any group. It was concluded the Cl- transport in CSF can be interfered with by use of blocking agents which inhibit Cl--HCO-3 exchange channels.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acid-Base Equilibrium; Animals; Bicarbonates; Blood-Brain Barrier; Chlorides; Dogs; Female; Hydrogen-Ion Concentration; Hypercapnia; Male; Pyridoxal Phosphate