The use of the ß-blocker Nebivolol and the naturally derived compounds Stevia, Goji berry, and Epicatechin to prevent cardiovascular damage in the DOCA-salt rat model of hypertension

Oxidative stress is a significant factor in the pathogenesis of the DOCA-salt hypertensive rat, producing significantly diminished cardiovascular function. Treatments targeting oxidative stress have been very effective in this model, providing improvements in oxidative stress, cardiac function, vascular function and also remodelling within these tissues. Many plant derived compounds have intrinsic antioxidant properties, and can achieve very significant effects within disease models of oxidative stress. Extracts from the plants Stevia rebaudiana and Lycium barbarum are two compounds that exhibit promise in targeting the pathological processes underlying hypertension within the DOCA-salt model. The key finding of the studies within this thesis are that extracts from both of these plants improve electrophysiological remodelling within the DOCA-salt heart. Epicatechin, a compound found in cocoa and green tea, has been shown to reduce blood pressure in hypertensive human patients. However, its ability to provide cardioprotection in hypertension, especially within the DOCA-salt model, had previously not been assessed. This thesis presents evidence that epicatechin was effective in preventing an increase in diastolic stiffness associated with the DOCA-salt model and significantly reduce blood pressure. It is not only natural compounds that provide novel avenues for targeting oxidative stress, but the newer generations of !-blockers have also been shown to affect antioxidant pathways. The 3rd generation ß-blocker Nebivolol is a ß₁ selective antagonist that is also able to increase nitric oxide bioavailability by mechanisms that are not fully elucidated but are currently attributed to ß2 and ß3 effects. The work contained in this thesis provides evidence that although 0.5mg.kg