Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this be...Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.展开更多
Objective To investigate the effects of novel selective phosphodiesterase4 (PDE4) inhibitors,Ariflo and SB242126A, on the endothelin-1 (ET-1) - induced contractility occurring in nonpregnant human myome-trium specimen...Objective To investigate the effects of novel selective phosphodiesterase4 (PDE4) inhibitors,Ariflo and SB242126A, on the endothelin-1 (ET-1) - induced contractility occurring in nonpregnant human myome-trium specimens. Methods Contractile responses to Ariflo and SB242126A were recorded cumulatively on isola-ted human longitudinal myometrium specimens obtained through surgical operations. Results Ariflo andSB242126A could inhibit both the frequency and amplitude of spontaneous contractions of myometrium (pD2 =8. 6and 7. 6,n =4) and ET-1 -induced contractions in a concentration-dependent manner (pD2 = 7. 7 and 8. 1 ,n =5) ,with a potency similar to that of Rolipram. Conclusion Ariflo and SB242126A have an obvious inhibitory effecton endothelin-1-induced contractility of isolated human myometrium. The finding suggested that PDE4 inhibitorsmight have clinical potential in treating preterm labour and dysmenorrhoea.展开更多
文摘Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.
基金Supported by the grant of Sino-France Cooperation of INSERM and SSMU.
文摘Objective To investigate the effects of novel selective phosphodiesterase4 (PDE4) inhibitors,Ariflo and SB242126A, on the endothelin-1 (ET-1) - induced contractility occurring in nonpregnant human myome-trium specimens. Methods Contractile responses to Ariflo and SB242126A were recorded cumulatively on isola-ted human longitudinal myometrium specimens obtained through surgical operations. Results Ariflo andSB242126A could inhibit both the frequency and amplitude of spontaneous contractions of myometrium (pD2 =8. 6and 7. 6,n =4) and ET-1 -induced contractions in a concentration-dependent manner (pD2 = 7. 7 and 8. 1 ,n =5) ,with a potency similar to that of Rolipram. Conclusion Ariflo and SB242126A have an obvious inhibitory effecton endothelin-1-induced contractility of isolated human myometrium. The finding suggested that PDE4 inhibitorsmight have clinical potential in treating preterm labour and dysmenorrhoea.
