The inhibitory effect of diuretics on carbonic anhydrases.
A classification of diuretics mainly comprises mercurials; carbonic anhydrase inhibitors, thiazide diuretics, loop diuretics, inhibitors of renal epithelial Na+ channels and antagonists of mineralocorticoid receptors. We studied in this paper the relationship between diuretics and carbonic anhydrase (CA). Our in vitro and in vivo results show that all diuretics inhibit carbonic anhydrase II and renal CA IV. Further, our data show that they also inhibit epithelial cell CA in the renal tubules. The changes in intracellular 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 diuretics), Na+ channel blocking in distal and collecting tubules (amiloride, triamterene), as well as the antagonism between spironolactone and aldosterone at the mineralocorticoid receptor level, suggest that this competition might also be produced on CA II and on renal CA IV, which, in turn, could be influenced by pH-induced changes, the binding of the diuretic to its membrane receptor as well as the activity of the brush membrane or cytosolic pump. Furosemide and indapamide, diuretics known to have vasodilating effects, induce the fall of blood pressure that parallels the decrease of CA I activity. 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 diuretics. All diuretics inhibit CA isozymes.
Puscas
I
I
University of Medicine Oradea, Romania. ccam@.netcompsj.ro
Coltau
M
M
Baican
M
M
Pasca
R
R
Domuta
G
G
D000368:Aged; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000145:classification / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000097:blood / Q000378:metabolism; D004232:Diuretics / Q000145:classification / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008875:Middle Aged; D013552:Swine
D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D007527:Isoenzymes; D002256:Carbonic Anhydrases