Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, Kþ-depleted rats, a model of hypoPP, were administered 5.6 mgkg1 day1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated Kþ- depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from Kþ- depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of Kþ-depleted rats compared with that found in muscles from normokalemic rats. After treatment of Kþ-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of Kþ-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in Kþ-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA

Acetazolamide prevents vacuolar myopathy in skeletal muscle of K+-depleted rats

TRICARICO, Domenico;MELE, ANTONIETTA;CONTE, Diana;Lovaglio, S.;ROTONDO, GIULIO
2008

Abstract

Background and purpose: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux of lactate from skeletal muscle were also investigated. Experimental approach: For 10 days, Kþ-depleted rats, a model of hypoPP, were administered 5.6 mgkg1 day1 of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro lactate efflux measurements were performed in skeletal muscles from treated and untreated Kþ- depleted rats, and also from normokalemic rats. Key results: About three times as many vacuoles were found in the type II fibres of tibialis anterioris muscle sections from Kþ- depleted rats as were found in the same muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate on in vitro incubation was found in muscles of Kþ-depleted rats compared with that found in muscles from normokalemic rats. After treatment of Kþ-depleted rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle decreased to near normal values. Incubation with acetazolamide in vitro inhibited efflux of lactate from muscles of Kþ-depleted rats. In contrast, bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy after treatment in vivo and failed to inhibit lactate efflux in vitro. Conclusions and implications: Acetazolamide prevents vacuolar myopathy in Kþ-depleted rats. This effect was associated with inhibition of lactate transport, rather than inhibition of CA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/126064
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