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 (
M
‐
ANP
), 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
M
‐
ANP
(n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (
MAP
) was reduced by
M
‐
ANP
(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
M
‐
ANP
(12±2 to 6±2 mm Hg,
P
<0.05) and nitroglycerin (12±1 to 6±1 mm Hg,
P
<0.05).
M
‐
ANP
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
(
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
32 articles.
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