The inhibitory effect of diuretics on carbonic anhydrases

A classification of diuretics mainly comprises mercurials; carbonic anhydra se inhibitors, thiazide diuretics, loop diuretics, inhibitors of renal epit helial Na+ channels and antagonists of mineralocorticoid receptors. We stud ied in this paper the relationship between diuretics and carbonic anhydrase (CA). Our in vitro and in vivo results show that all diuretics inhibit car bonic anhydrase II and renal CA IV. Further, our data show that they also i nhibit epithelial cell CA in the renal tubules. The changes in intracellula r pH (pHi) induced by these diuretics through CA inhibition would influence : a) the coupling to their receptors affecting information transmission to the epithelial cells of renal tubules as well as diuretic response; b) the decrease of Na+ exchanger (thiazide), of Na+-K+-2Cl(-) relation (loop diure tics), Na+ channel blocking in distal and collecting tubules (amiloride, tr iamterene), as well as the antagonism between spironolactone and aldosteron e at the mineralocorticoid receptor level, suggest that this competition mi ght also be produced on CA II and on renal CA IV, which, in turn, could be influenced by pi-I-induced changes, the binding of the diuretic to its memb rane receptor as well as the activity of the brush membrane or cytosolic pu mp. Furosemide and indapamide, diuretics known to have vasodilating effects , induce the fall of blood pressure that parallels the decrease of CA I act ivity. These results show the involvement of CA in the mechanism of action of the diuretics and in their actions associated with vasodilating effects. pH changes resulting from the action of CA contribute to the action of diu retics. All diuretics inhibit CA isozymes.