Pharmacological PARP-1 Inhibition Against Hypertensive Target Organ Damage in a Chronic Animal Model

Abstract

Arterial hypertension represents a major cardiovascular epidemic condition, with a prevalence of more than 25% throughout the adult population, affecting nearly one billion individuals around the globe. It remains asymptomatic until later in its course, but as a long-term consequence of this condition, accumulating damage in specific organs propagates the development of cardiac pathologies, renal failure, cerebrovascular pathologies and vascular dementia, atherosclerotic vascular disease and retinopathy. Several processes are involved in these pathogenic alterations including endothelial activation, growth and migration of vascular smooth muscle cells, expression of pro-inflammatory mediators, changes in collagen turnover and the remodeling of extracellular matrix. Complex biochemical, hormonal and hemodynamic mechanisms form the basis of these alterations, referred as hypertensive target organ damage, however, the common ground is the excess generation of reactive oxygen species/ROS2, which, in addition to governing these pathological changes, possesses direct damaging properties6. Additional factors accompanying chronic hypertension may amplify these processes, including arterial stiffness, effects of sympathetic over-activity, dysregulation of tissue perfusion and increased activity of several hormone systems, especially the renin-angiotensinaldosterone system/RAAS2.