title: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action.
abstract: Five years ago, our in vitro and in vivo studies demonstrated for the first time that diuretic agents such as furosemide, hydrochlorothiazide, amiloride, triamterene and spironolactone inhibit carbonic anhydrase (CA) I, II and renal CA IV by a direct mechanism of action. In this paper we investigate the relationship between diuretics and CA I in the vasodilatory mechanism. Both in vitro (on purified CA I, erythrocyte CA I and smooth muscle CA I) and in vivo (in human and rabbits) we studied the effect of acetazolamide, hydrochlorothiazide, indapamide, furosemide, amiloride and triamterene on purified CA I, on human erythrocyte CA I, as well as on CA I isolated from vascular smooth muscle. Our results demonstrate that in vitro all diuretics inhibit CA I by a direct mechanism of action. Inhibition reached 100% with acetazolamide, 45% with hydrochlorothiazide, 82% with indapamide, 85% with furosemide, 68% with amiloride and 58% with triamterene. In vivo, similar inhibition of erythrocyte and smooth muscle CA I was obtained, being parallel with a reduction in arterial blood pressure values. Our data show that in addition to their already known mechanisms, diuretics also inhibit CA in vascular smooth muscle. Our results suggest that this mechanism is achieved by means of pH changes induced by CA I inhibition.
authors.affiliation: Romanian Academy of Medical Sciences, Simleu Silvaniei Center for Research and Medical Care, Salaj, Romania. ccam@teli.netcompsj.ro
authors.forename: I
authors.initials: I
authors.lastname: Puscas
authors.forename: M
authors.initials: M
authors.lastname: Coltau
authors.forename: M
authors.initials: M
authors.lastname: Baican
authors.forename: G
authors.initials: G
authors.lastname: Domuta
authors.forename: A
authors.initials: A
authors.lastname: Hecht
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000368:Aged; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000502:physiology*; D004232:Diuretics / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology*; D011817:Rabbits; D014223:Triamterene / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D006852:Hydrochlorothiazide; D000584:Amiloride; D005665:Furosemide; D002256:Carbonic Anhydrases; D007190:Indapamide; D000086:Acetazolamide; D014223:Triamterene