M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

Author:

McKie Paul M.1,Cataliotti Alessandro1,Ichiki Tomoko1,Sangaralingham S. Jeson1,Chen Horng H.1,Burnett John C.1

Affiliation:

1. Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN

Abstract

Background Systemic hypertension is a common characteristic in acute heart failure ( HF ). This increasingly recognized 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 ( MANP ), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase ( sGC ) activator. Methods and Results HF was induced by rapid RV pacing (180 beats per minute) 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 following intravenous MANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure ( MAP ) was reduced by MANP (139±4 to 118±3 mm Hg, P <0.05) and nitroglycerin (137±3 to 116±4 mm Hg, P <0.05); similar findings were recorded for pulmonary wedge pressure ( PCWP ) with MANP (12±2 to 6±2 mm Hg, P <0.05) and nitroglycerin (12±1 to 6±1 mm Hg, P <0.05). MANP enhanced renal function with significant increases ( P <0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P <0.05), whereas nitroglycerin had no significant ( P >0.05) effects on these renal parameters or aldosterone activation. Conclusions Our results advance the differential cardiorenal actions of pGC ( MANP ) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make MANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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