natriuretic-peptide--c-type and Cardiomegaly

Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin-angiotensin-aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on the complex network leading to cardiac hypertrophy, ventricular dysfunction, and transition to heart failure, and in the attempt to develop novel therapeutic agents. The aim of the present article is to review well-characterized molecular mechanisms underlying the antihypertrophic and antifibrotic effects of NPs in the heart that appear to be mainly mediated by guanylyl cyclase type A receptor. In particular, we discuss the calcineurin/NFAT, the sodium exchanger NHE-1, and the TGFβ1/Smad signaling pathways. The role of guanylyl cyclase type B receptor, along with the emerging functional significance of natriuretic peptide receptor type C as mediators of CNP antihypertrophic and antifibrotic actions in the heart are also considered.

Topics: Animals; Calcineurin; Cardiomegaly; Fibrosis; Humans; Myocardium; Natriuretic Peptide, C-Type; Natriuretic Peptides; NFATC Transcription Factors; Signal Transduction; Smad Proteins; Sodium-Hydrogen Exchangers; Transforming Growth Factor beta1

Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function.

Topics: Animals; Cardiomegaly; Cardiovascular Physiological Phenomena; Cardiovascular System; Guanylate Cyclase; Humans; Models, Biological; Natriuretic Peptide, C-Type; Receptors, Atrial Natriuretic Factor; Signal Transduction

Within the last five years, assay systems for measurement of plasma levels of brain natriuretic peptide (BNP) have been approved as a diagnostic aid for heart failure (HF). Similarly, nesiritide, a recombinant form of human BNP, has been approved for the treatment of acutely decompensated HF. Both BNP as a diagnostic test and a therapeutic modality are rapidly becoming integrated into clinical practice. The purpose of this review is to provide a brief overview of the physiology of the natriuretic peptides relevant to their informed clinical use. The current literature regarding the utility of measuring BNP for the diagnosis and management of HF is reviewed and practical recommendations regarding the interpretation of BNP levels are offered. The clinical literature regarding the use of recombinant BNP for the treatment of HF is reviewed, underscoring current gaps in our knowledge regarding the indications for and benefits of this novel agent.

Topics: Atrial Natriuretic Factor; Cardiomegaly; Diuresis; Heart Failure; Humans; Kidney; Myocardial Infarction; Natriuresis; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; ROC Curve; Survival Analysis; Treatment Outcome; Vasodilation; Ventricular Remodeling

Excessive activation of the sympathetic nervous system is involved in cardiovascular damage including cardiac hypertrophy. Natriuretic peptides are assumed to exert protective actions for the heart, alleviating hypertrophy and/or fibrosis of the myocardium. In contrast to this assumption, we show in the present study that both atrial and C-type natriuretic peptides (ANP and CNP) potentiate cardiac hypertrophic response to noradrenaline (NA) in rats. Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 micro-g/h NA without or with persistent intravenous administration of either 1.0 micro-g/h ANP or CNP for 14 days. Blood pressure (BP) was recorded under an unrestrained condition by a radiotelemetry system. Cardiac hypertrophic response to NA was evaluated by heart weight/body weight (HW/BW) ratio and microscopic measurement of myocyte size of the left ventricle. Mean BP levels at the light and dark cycles rose by about 20 mmHg following NA infusion for 14 days, with slight increases in HW/BW ratio and ventricular myocyte size. Infusions of ANP and CNP had no significant effects on mean BP in NA-infused rats, while two natriuretic peptides potentiated cardiac hypertrophic response to NA. Cardiac hypertrophy induced by co-administration of NA and ANP was attenuated by treatment with prazosin or atenolol. In summary, both ANP and CNP potentiated cardiac hypertrophic effect of continuously infused NA in rats, suggesting a possible pro-hypertrophic action of natriuretic peptides on the heart.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Male; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Norepinephrine; Rats; Rats, Wistar

Topics: Cardiomegaly; Exudates and Transudates; Heart Failure; Humans; Hydrostatic Pressure; L-Lactate Dehydrogenase; Natriuretic Peptide, C-Type; Pleural Effusion; Sensitivity and Specificity; Thoracentesis

Mitochondrial dysfunction has been implicated as a cause of energy deprivation in heart failure (HF). Herein, we tested individual and combined effects of two pathogenic factors of nonischemic HF, inhibition of nitric oxide synthesis [with l-N(G)-nitroarginine methyl ester (l-NAME)] and hypertension [with angiotensin II (AngII)], on myocardial mitochondrial function, oxidative stress, and metabolic gene expression. l-NAME and AngII were administered individually and in combination to mice for 5 wk. Although all treatments increased blood pressure and reduced cardiac contractile function, the l-NAME + AngII group was associated with the most severe HF, as characterized by edema, hypertrophy, oxidative stress, increased expression of Nppa and Nppb, and decreased expression of Atp2a2 and Camk2b. l-NAME + AngII-treated mice exhibited robust deterioration of cardiac mitochondrial function, as observed by reduced respiratory control ratios in subsarcolemmal mitochondria and reduced state 3 levels in interfibrillar mitochondria for complex I but not for complex II substrates. Cardiac myofibrils showed reduced ADP-supported and oligomycin-inhibited oxygen consumption. Mitochondrial functional impairment was accompanied by reduced mitochondrial DNA content and activities of pyruvate dehydrogenase and complex I but increased H2O2 production and tissue protein carbonyls in hearts from AngII and l-NAME + AngII groups. Microarray analyses revealed the majority of the gene changes attributed to the l-NAME + AngII group. Pathway analyses indicated significant changes in metabolic pathways, such as oxidative phosphorylation, mitochondrial function, cardiac hypertrophy, and fatty acid metabolism in l-NAME + AngII hearts. We conclude that l-NAME + AngII is associated with impaired mitochondrial respiratory function and increased oxidative stress compared with either l-NAME or AngII alone, resulting in nonischemic HF.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiomegaly; DNA, Mitochondrial; Electron Transport Complex I; Electron Transport Complex II; Enzyme Inhibitors; Gene Expression; Heart; Heart Failure; Hydrogen Peroxide; Mice; Mitochondria, Heart; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidative Stress; Protein Precursors; Pyruvate Dehydrogenase Complex; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Vasoconstrictor Agents

Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Cardiomegaly; Cell Line; Gene Expression; Gene Expression Regulation; Histone Deacetylase Inhibitors; Hydroxamic Acids; Imidazoles; Isoproterenol; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Myocytes, Cardiac; Natriuretic Peptide, C-Type; Nuclear Proteins; Protein Precursors; Tetrazoles; Trans-Activators

Both natriuretic peptides and nitric oxide may be protective in cardiac hypertrophy, although their functional effects are diminished in hypertrophy. Hypoxia inducible factor-1 (HIF-1) may also protect in cardiac hypertrophy. We hypothesized that upregulation of HIF-1 would protect the functional effects of cyclic GMP (cGMP) signaling in hypertrophied ventricular myocytes.. A cardiac hypertrophy model was created in mice by transverse aorta constriction. HIF-1 was increased by deferoxamine (150 mg/kg for 2 days). HIF-1alpha protein levels were examined. Functional parameters were measured (edge detector) on freshly isolated myocytes at baseline and after BNP (brain natriuretic peptide, 10(-8)-10(-7)M) or CNP (C-type natriuretic peptide, 10(-8)-10(-7)M) or SNAP (S-nitroso-N-acetyl-penicillamine, a nitric oxide donor, 10(-6)-10(-5)M) followed by KT5823 (a cyclic GMP-dependent protein kinase (PKG) inhibitor, 10(-6)M). We also determined PKG expression levels and kinase activity.. We found that under control conditions, BNP (-24%), CNP (-22%) and SNAP (-23%) reduced myocyte shortening, while KT5823 partially restored function. Deferoxamine treated control myocytes responded similarly. Baseline function was reduced in the myocytes from hypertrophied heart. BNP, CNP, SNAP and KT5823 also had no significant effects on function in these myocytes. Deferoxamine restored the negative functional effects of BNP (-22%), CNP (-18%) and SNAP (-19%) in hypertrophic cardiac myocytes and KT5823 partially reversed this effect. Additionally, deferoxamine maintained PKG expression levels and activity in hypertrophied heart.. Our results indicated that the HIF-1 protected the functional effects of cGMP signaling in cardiac hypertrophy through preservation of PKG.

Topics: Animals; Carbazoles; Cardiomegaly; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Deferoxamine; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nitric Oxide; S-Nitroso-N-Acetylpenicillamine; Signal Transduction; Up-Regulation

We tested the hypothesis that the negative inotropic effects of C-type natriuretic peptide (CNP) would be diminished in renal hypertensive (one-kidney-one-clip, 1K1C) hypertrophic rabbit hearts and that this attenuated effect would be due either to decreased cyclic GMP production or to reduced signaling.. Using isolated control and 1K1C ventricular myocytes, cell shortening data (video edge detection) were collected: (1) at baseline and after CNP 10(-8,-7) M, followed by KT5823 (KT), a cyclic GMP-dependent protein kinase inhibitor; or (2) at baseline, following KT pre-treatment and subsequent CNP 10(-8,-7) M. In addition, cyclic GMP levels were determined by radioimmunoassay at baseline and CNP 10(-7) M.. In control myocytes, CNP decreased percent shortening (5.7 +/- 0.4 versus 4.0 +/- 0.4% at 10(-7) M), maximal rate of shortening (58.7 +/- 5.1 versus 45.2 +/- 3.6 microm/sec) and maximal rate of relaxation (57.1 +/- 4.9 versus 44.1 +/- 3.4 microm/sec) in a concentration-dependent manner. These effects were attenuated by subsequent KT administration. CNP failed to produce these negative functional effects in 1K1C myocytes. When pre-treated with KT, CNP had no negative functional effect in either normal and 1K1C myocytes. Basal levels of cyclic GMP were similar in control versus 1K1C myocytes; however, CNP produced a significant rise in cyclic GMP level in control (63.6 +/- 7.8 versus 83.5 +/- 11.3 pmol/10(5) myocytes) but not in 1K1C (49.2 +/- 2.6 versus 52.7 +/- 5.6) myocytes.. Thus, CNP acted through the cyclic GMP protein kinase in control myocytes. We conclude that in hypertrophic cardiac myocytes, the decreased effect of CNP was because of decreased production of cyclic GMP.

Topics: Animals; Carbazoles; Cardiomegaly; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Disease Models, Animal; Guanylate Cyclase; Heart Ventricles; Hypertension, Renal; Hypertrophy; Indoles; Myocardial Contraction; Myocytes, Cardiac; Natriuretic Peptide, C-Type; Protein Kinase Inhibitors; Rabbits; Signal Transduction; Surgical Instruments

Increases in the myocardial level of cGMP usually exert negative inotropic effects in the mammalian hearts. We tested the hypothesis that the negative functional effects caused by nitric oxide (NO) or C-type natriuretic peptide (CNP) through cGMP would be blunted in hypertrophied cardiac myocytes. Contractile function, guanylyl cyclase activity, cGMP-dependent protein phosphorylation, and calcium transients were assessed in ventricular myocytes from aortic stenosis-induced hypertrophic and age-matched control mice. Basal percentage shortening was similar in control and hypertrophic myocytes. S-nitroso-N-acetyl-penicillamine (SNAP, an NO donor, 10(-6) and 10(-5) M) or CNP (10(-8) and 10(-7) M) reduced percentage shortening in both groups, but their effects were blunted in hypertrophic myocytes. Maximal rates of shortening and relaxation were depressed at the basal level, and both reagents had attenuated effects in hypertrophy. Similar results were also found after treatment with guanylin and carbon monoxide, other stimulators of particulate, and soluble guanylyl cyclase, respectively. Guanylyl cyclase activity was not significantly changed in hypertrophy. Addition of Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine (an inhibitor of cGMP-dependent protein kinase, 5 x 10(-6) M) blocked SNAP or the effect of CNP in control mice but not in hypertrophy, indicating the cGMP-dependent kinase (PKG) may not mediate the actions of cGMP induced by NO or CNP in the hypertrophic state. Calcium transients after SNAP or CNP were not significantly changed in hypertrophy. These results suggest that in hypertrophied mice, diminished effects of NO or CNP on ventricular myocyte contraction are not due to changes in guanylyl cyclase activity. The data also indicated that PKG-mediated pathways were diminished in hypertrophied myocardium, contributing to blunted effects.

Topics: Animals; Aortic Valve Stenosis; Blood Pressure; Cardiomegaly; Cyclic GMP; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocytes, Cardiac; Natriuretic Peptide, C-Type; Nitric Oxide; Organ Size

We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action.. Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes.. Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis.. C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region.. These data suggest that CNP may be useful as a novel antiremodeling agent.

Topics: Animals; Cardiomegaly; Fibrosis; Male; Myocardial Infarction; Natriuretic Peptide, C-Type; Rats; Rats, Sprague-Dawley; Ventricular Remodeling

C-type natriuretic peptide (CNP) is known to play a role in the local regulation of vascular tone. We recently found that CNP is also produced by cardiac ventricular cells. However, its local effect on myocyte hypertrophy remains to be elucidated. The present study investigated the effects of CNP on cultured cardiac myocyte hypertrophy and the interaction between CNP and endothelin-1 (ET-1) signaling pathways. CNP attenuated basal and ET-1-augumented protein synthesis, atrial natriuretic peptide secretion, hypertrophy-related gene expression, GATA-4 and MEF-2 DNA binding activities, Ca(2+)/calmodulin-dependent kinase II activity, and ERK phosphorylation. CNP also inhibited ET-1-induced increase in intracellular Ca(2+) concentration. These effects of CNP were mimicked by a cGMP analog, 8-bromo cGMP. However, the inhibitory effects of CNP on the hypertrophic response of myocytes were significantly diminished at high concentrations of ET-1. Although CNP increased intracellular cGMP levels in myocytes, ET-1 suppressed CNP-induced cellular cGMP accumulation. A protein kinase C activator and Ca(2+) ionophore mimicked this suppressive effect of ET-1. We further examined the effect of CNP on the paracrine action of ET-1 secreted from cardiac nonmyocytes. CNP and 8-bromo cGMP significantly inhibited ET-1 secretion from nonmyocytes. Although nonmyocyte-conditioned medium increased the protein synthesis in myocytes through endogenous ET-1 action, this increase was significantly attenuated by pretreatment of nonmyocytes with CNP and 8-bromo cGMP. These findings demonstrate that CNP inhibits ET-1-induced cardiac myocyte hypertrophy via a cGMP-dependent mechanism, and conversely, ET-1 inhibits CNP signaling by a protein kinase C- and Ca(2+)-dependent mechanism, suggesting mutual interference between CNP and ET-1 signaling pathways.

Topics: Animals; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Cardiomegaly; Cells, Cultured; Cyclic GMP; DNA; DNA-Binding Proteins; Drug Interactions; Endothelin-1; GATA4 Transcription Factor; MEF2 Transcription Factors; Mitogen-Activated Protein Kinases; Myocardium; Myogenic Regulatory Factors; Natriuretic Peptide, C-Type; Phosphorylation; Rats; Rats, Wistar; Signal Transduction; Transcription Factors

Atrial natriuretic peptide (ANP) prevents hypertrophy of neonatal cardiomyocytes. However, whether this effect is retained in the adult phenotype or if other members of the natriuretic peptide family exhibit similar antihypertrophic properties, has not been elucidated.. Our objective was to examine whether the natriuretic peptides protect against adult cardiomyocyte hypertrophy in vitro.. Adult rat cardiomyocytes were incubated with angiotensin II (Ang II)+/-ANP, B-type (BNP) or C-type (CNP) natriuretic peptides for determination of [3H]phenylalanine incorporation, c-fos mRNA expression and cyclic GMP. The effects of 8-bromo-cyclic GMP (cyclic GMP analogue), HS-142-1 (particulate guanylyl cyclase inhibitor) and KT5823 (cyclic GMP-dependent protein kinase inhibitor) were also investigated.. Ang II-stimulated increases in markers of hypertrophy, [3H]phenylalanine incorporation (to 136+/-3% of control, n=9) and c-fos mRNA expression (4.3+/-1.4-fold, n=5), were completely prevented by each of ANP, BNP or CNP. This protective action was accompanied by increased cardiomyocyte cyclic GMP. Inhibitory actions on [3H]phenylalanine incorporation were mimicked by 8-bromo-cyclic GMP, and were abolished by HS-142-1. KT5823 blocked the response to BNP and CNP, but not to ANP.. ANP prevents hypertrophy of adult rat cardiomyocytes. This protective action is shared by BNP and CNP and involves activation of particulate guanylyl cyclase receptors. Antihypertrophic effects of BNP and CNP are mediated through cyclic GMP-dependent protein kinase, but ANP can activate additional pathways independent of cyclic GMP to prevent adult cardiomyocte hypertrophy. These novel findings are of interest particularly since BNP appears to exert antifibrotic rather than antihypertrophic actions in vivo, while CNP is thought to act at least in part via the endothelium.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomegaly; Cyclic GMP; Drug Interactions; Guanylate Cyclase; Male; Muscle Cells; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor

It has been shown that atrial natriuretic peptide (ANP) influences proliferation of cardiac cells. To define the possible role of C-type natriuretic peptide (CNP) in cardiac hypertrophy, the influence of CNP on the secretion of ANP was studied with the use of perfused nonbeating atria from monocrotaline-treated rats. Increases in atrial volume caused proportional increases in ANP secretion that were markedly suppressed by CNP (10(-6) M) in nonhypertrophied left atria and control right atria but not in hypertrophied right atria. However, increases in atrial volume and mechanically stimulated extracellular fluid (ECF) translocation by CNP were similar to those in the control group. Therefore, the secretion of ANP in terms of ECF translocation was decreased by CNP in nonhypertrophied left and control right atria but not in hypertrophied atria. However, the inhibitory effect of 8-bromo-cGMP on the secretion of ANP was observed in both atria. The cGMP productions from perfused hypertrophied atria and their membranes exposed to CNP were significantly lower than those from nonhypertrophied atria. No significant difference in natriuretic peptide receptor-B transcript was found. Therefore, attenuation of the inhibitory effect of CNP on the ANP secretion in hypertrophied atria may be due to lack of cGMP production. The results showing the relief of CNP-induced negative inhibition of ANP secretion by atrial hypertrophy suggest that CNP may be a contributing factor to delay the development of cardiac hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Cyclic GMP; Extracellular Space; Guanylate Cyclase; Heart Atria; In Vitro Techniques; Male; Monocrotaline; Myocardium; Natriuretic Peptide, C-Type; Perfusion; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor