NON-CLASSICAL RAS THERAPEUTIC TARGETS FOR HYPERTENSIVE CARDIO-RENAL FIBROSIS

Abstract

Cardiovascular disease is the leading cause of death in the world. There is often high blood pressure-related end-organ damage causing stiffening of the heart and kidneys. This thesis has examined the ability of a number of new drugs to reverse organ stiffening and has found that stimulation of a non-classical angiotensin site reversed fibrosis in adult, but not aged, hypertensive rats due to excessive collagen build-up. Importantly, combination therapy did not impair renal function in aged hypertensive rats. Therefore, adverse renal effects are not likely to be a limiting factor in the translation of these newer angiotensin-related compounds to the clinic.