Abstract 16030: M-Atrial Natriuretic Peptide: A Novel Renal Enhancing Therapeutic in a Model of Heart Failure and Acute Hypertension
Introduction Systolic hypertension is an increasingly common characteristic among subjects with acute heart failure (HF). Importantly, an abrupt increase in blood pressure (BP) may be the mechanism for acute HF in such subjects often leading to renal as well as myocardial impairment. While the prevalence of hypertension in acute HF is up to 50%, current therapies are limited and there is an unmet need for renal enhancing therapies especially in the setting of hypertension and HF. M-atrial natriuretic peptide (M-ANP) is a novel natriuretic peptide based therapeutic with BP lowering, renal enhancing, and aldosterone inhibiting properties. In the current study we sought to define the actions of M-ANP as compared to nitroglycerin (NTG), which are both therapies mediated by the second messenger cGMP in a canine model of HF with hypertension.
Methods In a canine model, HF was induced by left ventricular (LV) pacing at 180 bpm for 10 days. On day 11 hypertension was induced by angiotensin II infusion. We characterized the cardiorenal and humoral actions of intravenous M-ANP (n=7) and NTG (n=7) and compared to placebo (n=7) in this model of HF with acute vasoconstrictive hypertension. *P<0.05.
Results The model of HF and acute vasoconstrictive hypertension is characterized by both impaired cardiac output* and elevated LV filling pressures*. Both M-ANP and NTG significantly reduced BP*, systemic vascular resistance*, and LV filling pressures* compared to placebo. However, the actions of M-ANP were more sustained (up to 120 minutes) compared to NTG. Further, M-ANP significantly increased renal blood flow*, glomerular filtration rate*, and natriuresis* and inhibited aldosterone* whereas NTG had no effect on renal or humoral parameters.
Discussion HF and hypertension is a common but underappreciated clinical entity with limited therapeutic options. M-ANP is a novel anti-hypertensive therapeutic with renal enhancing and aldosterone inhibiting properties. In the current study, M-ANP has similar but more sustained actions on BP and LV filling pressures when compared to NTG, a commonly used therapeutic in HF. Unlike NTG, M-ANP demonstrated renal enhancing properties. These results suggest M-ANP may there serve an unmet need for the treatment of HF and hypertension.
- © 2011 by American Heart Association, Inc.