Central and peripheral benzodiazepine ligands prevent mitochondrial damageinduced by noise exposure in the rat myocardium: An ultrastructural study

Noise represents an environmental stress factor affecting several organs an d apparatuses, including the cardiovascular system, In experimental animals undergoing noise exposure, subcellular myocardial changes have been report ed, especially at the mitochondrial level. In previous studies we found tha t diazepam, acting at both central and peripheral benzodiazepine receptors, prevented the onset of this myocardial damage,Ln the present study, we inv estigated the specific role played by central and/or peripheral benzodiazep ine receptors in preventing noise-induced myocardial alterations. In partic ular, the effect of clonazepam as a selective ligand for central sites, in comparison with the efficacy of Ligands selective for peripheral sites, suc h as Ro 5-4864 and PK-11195, was evaluated. Rats were pretreated with the t est drugs 30 min before exposure to noise for 6 or 12 hr and then sacrifice d. After fixing, samples of right atrium and ventricle were taken and proce ssed for either transmission or scanning electron microscopy. After 6 hr of noise exposure, only the atrium exhibited significant mitochondrial altera tions, whereas after 12 hr both atrium and ventricle were damaged. As expec ted, diazepam prevented noise-induced mitochondrial injury at both 6 and 12 hr. By contrast, clonazepam was effective only after 6 hr. The peripheral ligand PK-11195 attenuated mitochondrial damage at both 6 and 12 hr, wherea s Ro 5-4864 was effective only after 12 hr. In the present study, we confir m that noise exposure induces mitochondrial damage in the rat myocardium. D rugs acting at both central and peripheral benzodiazepine receptors signifi cantly prevent this damage. Differences in the amount and in the duration o f the protective effect might depend on variability in the potency and in t he pharmacokinetics of the specific drugs. Anat Rec 255:334-341, 1999. (C) 1999 Wiley-Liss, Inc.