Abstract
Purpose: Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly common phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP), a novel particulate guanylyl cyclase activator (pGC), and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. Methods: HF was induced by rapid right ventricular pacing (180 bpm) for 10 days. On day 11 hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and for 300 minutes following intravenous M-ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Results: Mean arterial pressure (MAP) was reduced by M-ANP (139±4 to 118±3mmHg, p 0.05) effects on these renal parameters or aldosterone activation. ![Figure][1] Conclusions: Our results advance the differential cardiorenal actions of pGC (M-ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M-ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal. [1]: pending:yes
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