MICRODIALYSIS ANALYSIS OF EFFECTS OF LOOP DIURETICS AND ACETAZOLAMIDEON CHLORIDE TRANSPORT FROM BLOOD TO CSF

With the hypothesis that the NaCl cotransporter in mammalian choroid p lexus (CP) has a role in CSF formation, we postulated that loop diuret ic agents would curtail transport of Cl from blood to CSF. Microdialys is in the cisterna magna of Sprague-Dawley rats was used to assess the ability of furosemide and ethacrynic acid (i.e. loop agents that inte rfere directly with cotransport) to inhibit Cl-36 transport from blood to CSF over a 3-h period. Cl uptake by CSF was quantified as % volume of distribution (V(d)) of Cl-36, i.e. 100 x cpm/g CSF divided-by cpm/ ml plasma. Uptake curves of V(d) vs. time were constructed for the var ious treatments; then, to compare drug effects, the curves were analyz ed for: (i) the early slope of uptake (K(in)), (ii) the steady-state v alue for V(d), and (iii) the area-under-curve (AUC). Assessment of the curve parameters collectively revealed that at 5 mg/kg, both furosemi de (FUR) and ethacrynic acid (EA) reduced Cl penetration into CSF by o ne quarter; at 50 mg/kg, these loop agents decreased Cl uptake by abou t a third. On the other hand, 50 mg/kg of the carbonic anhydrase inhib itor, acetazolamide, reduced Cl uptake into CSF by 55-60%. Thus, NaCl cotransport inhibitors maximally reduced Cl transport in the rat by ab out 35%; this inhibition was less extensive than that brought about by acetazolamide, which interferes with CSF secretion by a different mec hanism.