ISH PRE-2 THE VASCULAR PHENOTYPE IN HYPERTENSION - MOLECULAR MECHANISMS AND CLINICAL IMPLICATIONS.

Pathophysiological mechanisms contributing to hypertension include endothelial dysfunction and vascular ignalling. These changes are initially adaptive but chronically become maladaptive leading to vascular damage and loss of function. Common to these processes are changes in the characteristics of vascular cells to a pro-infl ammatory, vasoconstrictory and proliferative phenotype, infl uenced by activation of the RAS and oxidative stress. Increased ROS production and decreased cellular antioxidant defense mechanisms, contribute to oxidative stress, which infl uences redox-sensitive Ang II ignalling that promotes vascular injury in hypertension. Clinical studies demonstrate that improved vascular function is associated with reduced hypertension-related target-organ damage. Accordingly approaches to promote vascular health should be a therapeutic priority. Such strategies include conventional antihypertensive drugs and lifestyle modifi cations, which reduce oxidative stress and dampen activation of injurious ignalling pathways. Novel approaches, such as Nox inhibitors, agents that increase antioxidant capacity (e.g. Nrf-2 activators), anti-infl ammatory immune-modulators and elements of counter-regulatory axis of the RAS, namely AT2R, Ang-(1-7) and Mas receptors, have potential in promoting vascular health and reducing blood pressure. This presentation highlights some molecular and cellular mechanisms that underlie vascular injury in hypertension, and focuses on strategies to ameliorate vascular damage. Novel concepts relating to redox ignalling will be discussed. By elucidating sub-cellular mechanisms new disease-specifi c vascular molecules will be identifi ed for development of innovative therapies to prevent/regress injury and thereby improve management of hypertension and associated target organ damage.