AW-APSH-1: TARGETING WINDOWS OF PLASTICITY TO PREVENT HYPERTENSION.

Abstract

Failing lifestyle interventions, there are many classes of anti-hypertensive drugs that are highly effective in most patients if taken appropriately. But multiple agents taken daily may be required to achieve target blood pressure (BP). The problem is that the majority of patients are non-compliant: they do not take their drugs continuously, choose to only take some, or stop taking them completely. It is time to focus on interventions that do not require lifelong daily medications, and this requires understanding and treating the causative factors. For decades, it has been understood that the kidney, under the influence of both the renin-angiotensin-aldosterone system and sympathetic nerves, has a dominant role in the long-term control of extracellular fluid volume and BP. The kidney is an important target for the treatment of hypertension. Early postnatal life is a period of remarkable plasticity and is a neglected window of opportunity to prevent disease onset. Our aim is to preserve and protect function of existing nephrons. If born with reduced renal mass (less nephrons), the compensatory response is to increase the filtration rate of each individual nephron so that GFR is maintained. Clinically, the degree of nephron overload is linked to faster age and disease related reduction in renal functional reserve, glomerular damage, albuminuria and hypertension. By targeting the postnatal period of maturation, our aim is to prevent maladaptive compensatory hypertrophy and hyperfiltration to preserve kidney health-span without the need for lifelong drug therapy. Our studies in a large animal model of congenital renal mass reduction demonstrate the long-term therapeutic potential of a brief period of angiotensin converting enzyme inhibition early in life to alter the trajectory of renal and cardiovascular disease.