Exercise Training Attenuates Cardiac Vulnerability and Promotes Cardiac Resistance to Isoproterenol-Induced Injury Following Hookah Smoke Inhalation in Male Rats: Role of Klotho and Sirtuins.

Hookah smoking is on the rise around the world. Present study investigated the heart resistance to harmful stress following long-term waterpipe tobacco smoking (WTS) and moderate-intensity exercise training intervention in male Wistar rats. Animals were randomly divided into a non-ischemic heart control group and four ischemic heart groups including ISO (isoproterenol-treated), Ex + ISO (subjected to exercise plus ISO), S + ISO (exposed to hookah smoke plus ISO), and Ex + S + ISO (subjected to exercise along with hookah smoke plus ISO). After eight weeks of training and WTS, heart ischemia induced by isoproterenol injections. Then, cardiac functional indices and some biochemical and histopathological parameters were assessed. WTS + ISO reduced systolic pressure, ± dP/dt max, and contractility indices (P < 0.001 vs. ISO group) and increased end diastolic pressure and Tau index (P < 0.001 vs. ISO) of the left ventricle. Also, WTS + ISO was associated with an increase in Bax protein level and Bax/Bcl-2 ratio (P < 0.05 and P < 001, respectively, vs. ISO group) as apoptotic markers of heart tissue. Hookah smoke significantly decreased SIRT1 (P < 0.05 and P < 0.001, respectively, vs. ISO) and klotho (P < 0.01 and P < 0.001, respectively, vs. ISO) in serum and heart, and SIRT3 and pS9-GSK-3β (P < 001 and P < 0.05, respectively, vs. ISO) in heart tissue. Combination of exercise with WTS prevented the hookah smoke-induced alterations in apoptotic markers, cardiac functional indices, and SIRT1, SIRT3, klotho, and pS9-GSK-3β proteins. The findings demonstrated that hookah smoke inhalation intensifies ventricular dysfunction and decreases heart resistance to harmful stresses. Moderate-intensity exercise training attenuated these complications partly through recovering the klotho and sirtuins levels and apoptosis-survival balancing.