Normal Atrial Natriuretic Peptide Research Articles

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis

SummaryTwo siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)–converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Cardiac Autophagy Deficiency Attenuates ANP Production and Disrupts Myocardial-Adipose Cross Talk, Leading to Increased Fat Accumulation and Metabolic Dysfunction.

Increased myocardial autophagy has been established as an important stress-induced cardioprotective response. Three weeks after generating cardiomyocyte-specific autophagy deficiency, via inducible deletion of autophagy-related protein 7 (Atg7), we found that these mice (AKO) had increased body weight and fat mass without altered food intake. Glucose and insulin tolerance tests indicated reduced insulin sensitivity in AKO mice. Metabolic cage analysis showed reduced ambulatory activity and oxygen consumption with a trend of elevated respiratory exchange ratio in AKO mice. Direct analysis of metabolism in subcutaneous and visceral adipocytes showed increased glucose oxidation and reduced ATGL expression and HSL phosphorylation with no change in lipid synthesis or fatty acid oxidation. Importantly, we found AKO mice had reduced myocardial and circulating levels of atrial natriuretic peptide (ANP), an established mediator of myocardial-adipose cross talk. When normal ANP levels were restored to AKO mice with use of osmotic pump, the metabolic dysfunction evident in AKO mice was corrected. We conclude that cardiac autophagy deficiency alters myocardial-adipose cross talk via decreased ANP levels with adverse metabolic consequences.

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP

ObjectivesThis study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF. BackgroundThe endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload. MethodsANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study’s goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3′,5′cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects. ResultsIn cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003). ConclusionsAmong a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

Atrial natriuretic peptide attenuates thrombin‐induced inflammation (672.4)

One microcirculatory homeostatic action of atrial natriuretic peptide (ANP) in the absence of inflammation is to increase barrier permeability to plasma proteins (Ps) when plasma volume is increased. However several investigations, particularly in cultured endothelial cells, suggest that high concentrations of ANP may also attenuate Ps. We tested the hypothesis that this action of ANP was characteristic of endothelium expressing a pro‐inflammatory phenotype. In individually perfused rat mesentery microvessels with no prior exposure to inflammation, pretreatment for 30 min with ANP (100 ng/ml) did not attenuate the increased permeability after exposure to bradykinin (10 nM). However in mouse skin where thrombin increased Ps 24 hours after an aseptic wound (AJP Heart, 296: 848, 2009), ANP added to the wound (50 ng/min/kg bw) significantly attenuated the thrombin induced transvascular albumin. At the same time, ANP attenuated thrombin induced neutrophil accumulation in the wound, and ANP alone increased Ps. Our results confirm that ANP acts to attenuate transvascular exchange in an intact microvasculature but only under inflammatory conditions. The mechanism of action appears to be independent of the normal ANP signaling pathways to increase Ps, and may involve reduced production of pro‐inflammatory agents from activated endothelium, neutrophils, or other inflammatory cells.Grant Funding Source: Supported by NIH HL28607

Atrial Natriuretic Peptide Affects Cardiac Remodeling, Function, Heart Failure, and Survival in a Mouse Model of Dilated Cardiomyopathy

Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

Lack of acute cyclosporine nephrotoxicity in late heart-transplant recipients

Background Cyclosporine induces daily renal hypoperfusion in subjects with normal atrial natriuretic peptide (ANP) levels, but its acute effects in heart transplant patients with increased ANP remain to be determined. Methods Cyclosporinemia and creatinine clearance were monitored during 7 hours following cyclosporine administration in 6 heart transplant patients. Results-conclusions No acute cyclosporine-induced decrease in creatinine clearance was observed after heart transplantation. These data suggest that maintenance cyclosporine dose may be less nephrotoxic than suspected and that increased ANP might protect the renal function late after heart transplantation.

Early diagnosis of ectopic arginine vasopressin secretion

We describe a patient who presented with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2 months before clinical evidence of bronchogenic malignancy. Because of the potential for the ectopic production of atrial natriuretic peptide (ANP) to mimic SIADH, both hormones were measured in this hyponatremic patient to seek a possible marker of tumor activity. A hypertonic saline infusion at presentation revealed excessive osmotically decoupled secretion of arginine vasopressin but a normal ANP response.

Atrial natriuretic peptide as a marker for doxorubicin-induced cardiotoxic effects.

Doxorubicin is an effective antineoplastic agent, but it frequently causes dose-related cardiotoxic effects. Because the atrial natriuretic peptide (ANP) level is elevated in children with heart defects, the authors measured the ANP levels in children to determine whether ANP might serve as a simple diagnostic indicator of cardiotoxic effects. Sixteen patients, 5 to 19 years of age, who were being treated with doxorubicin (45 mg/m2 body surface area) for various malignancies had ANP levels measured in plasma. There was a group of six children, with a significant peak of plasma ANP (pANP) levels 3 weeks after the administration of the drug. Of these six patients, five had received high cumulative doses of doxorubicin (160 to 370 mg/m2), and two of them went into congestive heart failure without a previous decline in left ventricular ejection fraction, a standard technique for monitoring cardiac function during treatment with doxorubicin. The other ten patients had normal ANP levels throughout the study, and signs of cardiac dysfunction did not develop. None of the patients in the control group who had cancer and were not treated with doxorubicin and none of the healthy volunteers had elevated ANP levels. These preliminary results suggest that pANP may be useful as an early and sensitive indicator for doxorubicin-related myocardial damage.

Heart Failure Augments the Cardiovascular and Renal Effects of Neutral Endopeptidase Inhibition in Rats

We compared the cardiovascular and renal actions of the neutral endopeptidase (NEP) inhibitor, SQ 28,603, in normal rats and in rats with healed myocardial infarcts. The infarcted rats were studied in the conscious state 8 weeks after ligation of the left main coronary artery and 4 h after placement of cardiovascular and renal catheters. Infarct size was 39 +/- 1.2% of left ventricle circumference; right ventricle and lung weight to body weight ratios were twice those of normal rats. These postmortem values were shown to be associated with elevated left ventricular end diastolic pressure and high plasma atrial natriuretic peptide (ANP) concentration in separate groups of rats. SQ 28,603 at 100 mumol/kg intravenously (i.v.) caused urine volume and sodium excretion to increase by 79 +/- 11 microliters/min and 8.2 +/- 1.4 microEq/min, respectively, 20 min after injection in infarcted rats; these changes were significantly greater than those in normal rats (12 +/- 5 microliters/min and 1.6 microEq/min, respectively). Thoracic venous pressure decreased by 1.9 +/- 0.4 mm Hg 80 min after SQ 28,603 in infarcted rats and by only 0.1 +/- 0.1 mm Hg in normal rats (p less than 0.05 vs. infarcted rats). SQ 28,603 had no effects on mean arterial pressure (MAP), cardiac output (CO), or glomerular filtration rate (GFR). The observation that NEP inhibition has more pronounced effects in animals with high ambient ANP level than in those with normal ANP is consistent with previous studies in a variety of animal models and supports the concept that NEP inhibition potentiates endogenous ANP.

Normal atrial natriuretic peptide release after acute and chronic stimuli in hypophysectomized rats

To test the hypothesis that the pituitary gland has a role in modulating the release of atrial natriuretic peptide (ANP) from atrial myocytes, we applied different stimuli of both acute and chronic nature to rats 8-10 days after hypophysectomy (Hypx). Acute rapid cardiac pacing at a rate of 500 beats/min in anesthetized rats caused a marked increase in plasma levels of ANP (from 76 +/- 7 to 237 +/- 60 pg/ml, P less than 0.05) despite a marked decrease of blood pressure. This response was similar to that of paced control rats, but because the basal levels were lower in Hypx rats, the relative increase in ANP was larger in the experimental group. Studies were also done in a chronic model of high-output congestive heart failure produced by an aortocaval fistula in hydrocortisone-supplemented rats. Although these rats had low blood pressure 2-3 days after surgery, there were marked increases in right atrial pressures associated with high plasma levels of ANP (194 +/- 24 pg/ml) that were not significantly different from controls (221 +/- 26 pg/ml, P greater than 0.05). These results indicate that the role of the pituitary in ANP release is indirect, and no specific hypophyseal factor is required for this response. Hemodynamic parameters are the important determinants of ANP secretion, even in hypophysectomized rats.

Effect of treatment with L-thyroxine on plasma levels of atrial natriuretic peptide (ANP) in athyreotic patients: indirect evidence for the necessity of adequate thyroid hormone levels to maintain normal ANP levels

Journal Article Effect of treatment with L-thyroxine on plasma levels of atrial natriuretic peptide (ANP) in athyreotic patients: indirect evidence for the necessity of adequate thyroid hormone levels to maintain normal ANP levels Get access M Weissel, M Weissel 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar C Punzengruber, C Punzengruber 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar E Hartter, E Hartter 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar O Burghuber, O Burghuber 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar B Ludvik, B Ludvik 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar W Woloszczuk W Woloszczuk 2. Department of Medicine, University of ViennaL. Boltzmann Institutes for Nuclear Medicine and Endocrinology Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 117, Issue 4_Supplement, Apr 1988, Page S158, https://doi.org/10.1530/acta.0.117S158 Published: 01 April 1988