Atrial Natriuretic Peptide Synthesis Research Articles

Plasma Corin: A New Biochemical Marker for Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder. Atrial natriuretic peptide (ANP) is a risk factor for PCOS. Corin protein has an essential role in ANP synthesis. This study aimed to evaluate corin as a sensitive biomarker for PCOS. A case-control study was conducted with 70 PCOS patients and 70 healthy females. Plasma Corin levels were quantified using enzyme-linked immunosorbent assay. The median plasma corin levels in PCOS patients and controls were 1785 and 822.5 pg/mL, respectively. Plasma corin levels were significantly elevated in PCOS patients than in the controls (p < 0.001). The optimal cut-off value was set at 1186 pg/mL. The sensitivity and specificity of Corin were 100% and 97.1%, respectively. Plasma corin levels were surrogate predictors for infertility in women with PCOS. It had an odds ratio of 5.9 (95% confidence interval: 1.1-32.7) (p = 0.04). Plasma corin levels were more highly detected in patients with PCOS than in the controls. Plasma corin level has reasonable diagnostic interpretation for PCOS. Corin appears as a worthy distinct predictor of infertility in PCOS women. Therefore, Corin may be a substantial biomarker for PCOS.

Whole Exome Sequencing Identified Mutations in Genes Involved in the Synthesis of Atrial Natriuretic Peptide from the Heart in Hypertensive Cardiovascular Disease Patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

(R,S)-Ketamine Promotes Striatal Neurogenesis and Sensorimotor Recovery Through Improving Poststroke Depression–Mediated Decrease in Atrial Natriuretic Peptide

BackgroundPoststroke social isolation could worsen poststroke depression and dampen neurogenesis. (R,S)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation–mediated depressive-like behaviors and sensorimotor recovery remain unclear. MethodsMice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days postischemia. ISO mice received 2 weeks of (R,S)-ketamine treatment starting at 14 days postischemia. Primary ependymal epithelial cells and choroid plexus epithelial cells were cultured and treated with recombinant human atrial natriuretic peptide (ANP) protein. ResultsThe poststroke social isolation model was successfully established using middle cerebral artery occlusion combined with poststroke isolation, as demonstrated by a more prominent depression-like phenotype in ISO mice compared with pair-housed mice. (R,S)-ketamine reversed ISO-mediated depressive-like behaviors and increased ANP levels in the atrium. The depression-like phenotype was negatively correlated with ANP levels in both the atrium and plasma. Atrial GLP-1 and GLP-1 receptor signaling was essential to the promoting effects of (R,S)-ketamine on the synthesis and secretion of ANP from the atrium in ISO mice. (R,S)-ketamine also increased ANP and TGF-β1 levels in the choroid plexus of ISO mice. Recombinant human ANP increased TGF-β1 levels in both the primarily cultured ependymal epithelial cells and choroid plexus epithelial cells. Furthermore, (R,S)-ketamine increased TGF-β1 levels in the ischemic hemisphere and promoted striatal neurogenesis and sensorimotor recovery via ANP in ISO mice. Conclusions(R,S)-ketamine alleviated poststroke ISO-mediated depressive-like behaviors and thus promoted striatal neurogenesis and sensorimotor recovery via ANP.

Chamber-specific regulation of atrial natriuretic peptide secretion in cardiac hypertrophy: atrial wall dynamics in the ANP secretion

The heart is involved in the regulation of blood pressure and body fluid homeostasis. As a blood volume sensor and effector for the regulation of the volume and pressure homeostasis, the atria are the central regulator to secrete humoral messenger cardiac natriuretic hormones into the circulation. The primary action of the atria in response to the volume change in the body is to control the secretion of atrial natriuretic peptide (ANP), a member of the family of cardiac natriuretic hormones. Although all cardiac chambers are able to secrete ANP, the major source of the cardiac hormone is the atria until reactivation of the synthesis of the ventricles. In heart disease including hypertension and cardiac hypertrophy, ventricular ANP synthesis and plasma levels of ANP are increased. However, the roles of the atria for the ANP secretion are not well defined in hypertension or heart failure. Under the high concentration of plasma levels of ANP by compensatory and/or pathophysiological reactivation of the ventricular synthesis and release of ANP, with activation of the renin-angiotensin system and changes in the atrial distensibility, the roles of the atria should be reevaluated in the heart disease. The purpose of the present review is to address modulation of the atrial role in the regulation of ANP secretion and its significance in the pathological changes in hypertension and cardiac disease and to strengthen the importance of the role of the interstitial fluid dynamics of the atrial wall in the regulation of ANP secretion.

Atrial secretion of ANP is suppressed in renovascular hypertension: shifting of ANP secretion from atria to the left ventricle.

In the present study, the change in secretion of atrial natriuretic peptide (ANP) from the atria was defined in hypertension accompanied by ventricular hypertrophy and increased synthesis of ANP. To identify the change of the secretion and mechanisms involved, experiments were performed in isolated perfused beating atria from sham-operated normotensive and renovascular hypertensive rats. Expression of ANP, natriuretic peptide receptor (NPR)-C, components of the renin-angiotensin system, and muscarinic signaling pathway was measured in cardiac tissues. Basal levels of ANP secretion and acetylcholine (ACh)- and stretch-induced activation of ANP secretion were suppressed in the atria from hypertensive compared with normotensive rats. ACh increased ANP secretion via M2 muscarinic ACh receptor-ACh-sensitive K+ channel signaling. In hypertensive rats, ANP concentration increased in the left ventricle but decreased in the right ventricle. The atrial concentration of ANP was not changed in hypertensive compared with normotensive rats. ANP mRNA expression was accentuated in the left ventricle but suppressed in the other cardiac chambers in the hearts of hypertensive rats. NPR-C expression was inversely related to ANP mRNA levels. Angiotensin II type 1 receptor (AT1R) expression was accentuated in the cardiac chambers from hypertensive rats compared with normotensive rats, whereas angiotensin II type 2 receptor, M2 muscarinic receptor, and Kir3.4 channels were suppressed. AT1R blockade with losartan reversed the change observed in hypertensive rats. The present findings indicate that renovascular hypertension shifts the major site of ANP secretion and synthesis from the atria to the left ventricle through modulation of the expression of ANP, NPR-C, AT1R, and the M2 muscarinic signaling pathway. NEW & NOTEWORTHY Renovascular hypertension suppresses the atrial secretion of ANP and shifts the major site of the regulation of ANP secretion and synthesis from atria to the hypertrophied left ventricle possibly via modulation of the expression of ANP, natriuretic peptide receptor-C, angiotensin II subtype 1 receptor, and M2 muscarinic signaling pathway.

Effect of oleanolic acid on the regulation of water, electrolyte and the renin system (701.4)

Effect of oleanolic acid on the regulation of water, electrolyte and the renin system Yoon Hee Choi1,2, Min Chul Kho1,2, Ji Hun Park2,3, Kyung Woo Cho1,2, Dae Gill Kang1,2,3, Ho Sub Lee1,2 1Professional graduate school of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 570‐749, Republic of Korea 2 Hanbang Body‐fluid Research Center, Wonkwang University, Shinyong‐dong, Iksan, Jeonbuk, 570‐749, Republic of Korea 3Department of Food Industry Convergence, Wonkwang University, Iksan, Jeonbuk 570‐749, Republic of Korea ABSTRACT Oleanolic acid is an active ingredient of variable plants including medicinal herbs and edible vegetables. Previously, it was shown that oral intake of oleanolic acid accentuates the atrial natriuretic peptide (ANP) system. Oleanolic acid increases cardiac ANP synthesis, plasma levels, and secretion. The purpose of the present study was to identify the effects of oleanolic acid on the regulation of fluid and electrolyte homeostasis and renal hormone balance. Experiments were performed in rats housed in metabolic cage and Oleanolic acid was administered orally everyday for 7 days. Oleanolic acid increased urinary excretion of Na+, Cl‐, and K+ . Oleanolic acid also increased urinary excretion of creatinine and clearance for creatinine. Furthermore, oleanolic acid suppressed plasma renin activity and renal renin contents. These findings suggest that oleanolic acid increases glomerular filtration rate and urinary excretion of water and electrolytes via suppression of the renin‐angiotensin system. Thus, this provides experimental evidence for beneficial effects of oleanolic acid in the cardiovascular system.Keyworlds : Oleanolic acid;Renin‐angiotensin system;Glomerular filtration rate;Urinary; Renin activity

Expression patterns of atrial natriuretic peptide and its receptors within the cochlear spiral ganglion of the postnatal rat

The spiral ganglion, which is primarily composed of spiral ganglion neurons and satellite glial cells, transmits auditory information from sensory hair cells to the central nervous system. Atrial natriuretic peptide (ANP), acting through specific receptors, is a regulatory peptide required for a variety of cardiac, neuronal and glial functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors (NPR-A and NPR-C) in the inner ear, their presence within the cochlear spiral ganglion and their regulatory roles during auditory neurotransmission and development is not known. Here we investigated the expression patterns and levels of ANP and its receptors within the cochlear spiral ganglion of the postnatal rat using immunofluorescence and immunoelectron microscopy techniques, reverse transcription-polymerase chain reaction and Western blot analysis. We have demonstrated that ANP and its receptors colocalize in both subtypes of spiral ganglion neurons and in perineuronal satellite glial cells. Furthermore, we have analyzed differential expression levels associated with both mRNA and protein of ANP and its receptors within the rat spiral ganglion during postnatal development. Collectively, our research provides direct evidence for the presence and synthesis of ANP and its receptors in both neuronal and non-neuronal cells within the cochlear spiral ganglion, suggesting possible roles for ANP in modulating neuronal and glial functions, as well as neuron–satellite glial cell communication, within the spiral ganglion during auditory neurotransmission and development.

Conjugated equine estrogens and estradiol benzoate differentially modulate the natriuretic peptide system in spontaneously hypertensive rats

The purpose of this study was to compare the effects of conjugated equine estrogens (CEE) and estradiol benzoate on the blood pressure and body weight of spontaneously hypertensive rats (SHRs) and the associated changes in several components of the natriuretic peptide system. The blood pressure of randomly distributed female SHRs and Wistar rats was determined by tail plethysmography. The rats were ovariectomized and, after 3 weeks, injected daily for 4 days with estradiol benzoate (5 μg/100 g/d), CEE (50 μg/100 g/d), or vehicle (corn oil 0.1 mL/100 g/d). One day after the last injection, the rats were decapitated, and their blood was collected to measure atrial natriuretic peptide (ANP) and estradiol. The atria were removed to measure ANP levels using radioimmunoassay and to quantify ANP messenger RNA expression using real-time polymerase chain reaction. The kidneys and adipose tissue were removed to analyze the expression of natriuretic peptide clearance receptor messenger RNA. A reduction in blood pressure was observed in estradiol-treated SHRs, but CEE treatment had no effect. Estradiol decreased the body weight and parametrial adipose tissue mass of SHRs. Estradiol-induced alterations in SHRs were accompanied by increased synthesis and release of ANP. CEE had no effect on body weight but increased the mesenteric adipose tissue mass of SHRs. These results indicate that estradiol and CEE have different effects on the reduction in body weight and blood pressure. These results are correlated with changes in plasma ANP levels.

Oleanolic acid increases plasma ANP levels via an accentuation of cardiac ANP synthesis and secretion in rats

Oleanolic acid is known to have beneficial effects on the regulation of cardiovascular homeostasis. The present study was designed to identify the effects of oleanolic acid on plasma levels and atrial synthesis and secretion of atrial natriuretic peptide (ANP). Experiments were performed in rats and isolated perfused beating rat atria. ANP was measured using a selective radioimmunoassay. ANP mRNA expression was measured using real-time quantitative polymerase chain reaction. Administration of oleanolic acid increased plasma ANP levels in a dose-related manner. Similarly, oleanolic acid increased atrial ANP content and ANP mRNA expression. To evaluate the effects of oleanolic acid on ANP secretion, atrial stretch and muscarinic acetylcholine receptor activation were applied to the atria from rats chronically treated with oleanolic acid. Baseline levels of ANP secretion were higher in the atria from rats treated with oleanolic acid compared to rats treated with vehicle. Furthermore, oleanolic acid treatment enhanced the stretch-induced increase in ANP secretion. Acetylcholine in the presence of isoproterenol increased ANP secretion. The acetylcholine-induced increase in ANP secretion was also enhanced in the atria from rats treated with oleanolic acid compared to atria from rats treated with vehicle. The present findings indicate that oleanolic acid increases plasma ANP levels via increased ANP synthesis and secretion in rats. It is proposed that an accentuation of the ANP system is involved in the beneficial effects of oleanolic acid on the regulation of cardiovascular homeostasis.

Expression and localization of atrial natriuretic peptide and its receptors in rat spiral ganglion neurons

Spiral ganglion neurons (SGNs) are the primary auditory neurons in the inner ear, conveying auditory information between sensory hair cells and the central nervous system. Atrial natriuretic peptide (ANP), acting through specific receptors, is a regulatory peptide required for a variety of cardiac and neuronal functions. While the localization of ANP and its receptors (NPR-A and NPR-C) in the inner ear has been widely studied, there is only limited information regarding their localization in cochlear SGNs and their regulatory roles during primary auditory neurotransmission. Here we have investigated the presence of ANP and its receptors in the cochlear spiral ganglion of the postnatal rat using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. ANP and its receptors are expressed in the cochlear SGNs at both the mRNA and protein level, and co-localize in the cochlear SGNs as shown by immunofluorescence. Our research provides a direct evidence for the presence and synthesis of ANP as well as its receptors in the cochlear SGNs, suggesting a possible role for ANP in modulating the neuronal functions of SGNs via its receptors.

Synthesis of atrial natriuretic peptide in the rabbit inner ear

Atrial natriuretic peptide (ANP) exhibits natriuretic, diuretic, and vasorelaxant activity, maintaining fluid and electrolyte homeostasis. Although ANP is mainly synthesized and secreted in/from atrium, ANP has been found in various tissues including the rat inner ear. The aim of this study was to identify the synthesis of ANP in lateral cochlear wall tissues and the presence of ANP in perilymph using rabbits. In vivo study using a rabbit model. Expression of ANP in the rabbit inner ear tissue and the presence of perilymph were examined by radioimmunoassay and polymerase chain reaction using an ANP polyclonal antibody and rat ANP primers, respectively. Characteristics of ANP and pro-ANP present in the inner ear were also evaluated by high-performance liquid chromatography (HPLC), comparing to rat cardiac ANP and pro-ANP. Immunoreactive ANP (ir-ANP) was found in the perilymph and lateral cochlear wall tissue of rabbits. The levels of ir-ANP in the perilymph were 5 to 16 ng/mL. Elusion profiles of HPLC showed two main peaks that were exactly matched with rat cardiac ANP and pro-ANP. Expression of ANP mRNA was also detected. Our findings suggest that ANP and its precursor protein are synthesized in the ear tissues and secreted to perilymph. This hormone may play a role in control of water and/or ion homeostasis of the fluids in the ear that are responsible for normal hearing.

Altered regulation of renal nitric oxide and atrial natriuretic peptide systems in angiotensin II-induced hypertension

The present study was aimed to determine whether there is an altered role of local nitric oxide (NO) and atrial natriuretic peptide (ANP) systems in the kidney in association with the angiotensin (Ang) II-induced hypertension. Male Sprague–Dawley rats were used. Ang II (100 ng·min − 1 ·kg − 1 ) was infused through entire time course. Thirteenth day after beginning the regimen, kidneys were taken. The protein expression of NO synthase (NOS) and nitrotyrosine was determined by semiquantitative immunoblotting. The mRNA expression of components of ANP system was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclases were determined by the amount of cGMP generated in responses to sodium nitroprusside and ANP, respectively. There developed hypertension and decreased creatinine clearance in the experimental group. The protein expression of eNOS, nNOS and nitrotyrosine was increased in the cortex, while that of iNOS remained unaltered. The urinary excretion of NO increased in Ang II-induced hypertensive rats. The catalytic activity of soluble guanylyl cyclase was blunted in the glomerulus in Ang II-induced hypertensive rats. The mRNA expression of ANP was increased in Ang II-induced hypertensive rats. Neither the expression of NPR-A nor that of NPR-C was changed. The protein expression of neutral endopeptidase was decreased and the activity of particulate guanylyl cyclase was blunted in the glomerulus and papilla in Ang II-induced hypertensive rats. In conclusion, the synthesis of NO and ANP was increased in the kidney of Ang II-induced hypertension, while stimulated cGMP response was blunted. These results suggest desensitization of guanylyl cyclase in the kidney of Ang II-induced hypertensive rats, which may contribute to the associated renal vasoconstriction and hypertension.

Adenosine kinase regulation of cardiomyocyte hypertrophy

There is evidence that extracellular adenosine can attenuate cardiac hypertrophy, but the mechanism by which this occurs is not clear. Here we investigated the role of adenosine receptors and adenosine metabolism in attenuation of cardiomyocyte hypertrophy. Phenylephrine (PE) caused hypertrophy of neonatal rat cardiomyocytes with increases of cell surface area, protein synthesis, and atrial natriuretic peptide (ANP) expression. These responses were attenuated by 5 μM 2-chloroadenosine (CADO; adenosine deaminase resistant adenosine analog) or 10 μM adenosine. While antagonism of adenosine receptors partially blocked the reduction of ANP expression produced by CADO, it did not restore cell size or protein synthesis. In support of a role for intracellular adenosine metabolism in regulating hypertrophy, the adenosine kinase (AK) inhibitors iodotubercidin and ABT-702 completely reversed the attenuation of cell size, protein synthesis, and expression of ANP by CADO or ADO. Examination of PE-induced phosphosignaling pathways revealed that CADO treatment did not reduce AKT(Ser⁴⁷³) phosphorylation but did attenuate sustained phosphorylation of Raf(Ser³³⁸) (24-48 h), mTOR(Ser²⁴⁴⁸) (24-48 h), p70S6k(Thr³⁸⁹) (2.5-48 h), and ERK(Thr²⁰²/Tyr²⁰⁴) (48 h). Inhibition of AK restored activation of these enzymes in the presence of CADO. Using dominant negative and constitutively active Raf adenoviruses, we found that Raf activation is necessary and sufficient for PE-induced mTORC1 signaling and cardiomyocyte hypertrophy. CADO treatment still blocked p70S6k(Thr³⁸⁹) phosphorylation and hypertrophy downstream of constitutively active Raf, however, despite a high level phosphorylation of ERK(Thr202/Tyr204) and AKT(Ser⁴⁷³). Reduction of Raf-induced p70S6k(Thr³⁸⁹) phosphorylation and hypertrophy by CADO was reversed by inhibiting AK. Together, these results identify AK as an important mediator of adenosine attenuation of cardiomyocyte hypertrophy, which acts, at least in part, through inhibition of Raf signaling to mTOR/p70S6k.

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system.

Potential renovascular hypertension, space missions, and the role of magnesium

Space flight (SF) and dust inhalation in habitats cause hypertension whereas in SF (alone) there is no consistent hypertension but reduced diurnal blood pressure (BP) variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute). There was no acute renal insult. Irwin's apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP) reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001) reductions of magnesium (Mg) required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%), endothelin, and catecholamine elevations (clearly shown in recent years) and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now.

Changes of Atrial Natriuretic Peptide System in Rats with Puromycin Aminonucleoside-Induced Nephrotic Syndrome

Sodium retention is a hallmark of nephrotic syndrome. We investigated whether sodium retention is associated with changes of natriuretic peptide system at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndrome. At day 7 after PAN (puromycin aminonucleoside) injection, the urinary excretion of sodium was decreased, along with the development of ascites and positive sodium balance. The plasma and urinary ANP (atrial natriuretic peptide) immunoreactivities were increased. ANP mRNA expression was increased in the heart and kidney, whereas that of NPR (natriuretic peptide receptor)-A and NPR-C mRNA was decreased in the kidney. The expression of NEP was decreased in the kidney. At day 14, urinary excretion of sodium did not differ from the control. The plasma ANP level and heart ANP mRNA expression returned to their control values. The expression of ANP mRNA in the kidney was increased in association with increased urinary ANP immunoreactivities. The expression of NPR-A in the kidney became normal, whereas that of NPR-C kept decreased. The expression of NEP (neutral endopeptidase) remained decreased. These findings suggest that the increased renal ANP synthesis in association with decreased metabolism via NEP and NPR-C may play a compensatory role against the development of sodium retention in nephrotic syndrome. The decreased of NPR-A expression in the kidney may contribute to the ANP resistance at day 7. The subsequent recovery of NPR-A expression may play a role in promoting sodium excretion in later stage (at day 14).

Impairment of the Natriuretic Peptide System in Follitropin Receptor Knockout Mice and Reversal by Estradiol: Implications for Obesity-Associated Hypertension in Menopause

Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

Alterations of atrial natriuretic peptide in cardiomyocytes and plasma of rats after different intensity exercise

To characterize the effect of long-term exercise training at different intensities on endocrine structure and function of the heart, plasma atrial natriuretic peptide (ANP) levels, expression of ANP in cardiomyocytes, and ultrastructure of cardiomyocytes were examined by radioimmunoassay, immunohistochemistry and transmission electron microscopy in Sprague-Dawley rats trained on a treadmill at different intensities for 8 weeks. The plasma ANP increased gradually with increasing exercise intensity. The immunoreactivity of ANP in cardiomyocytes increased in the moderate- and high-intensity exercise group and decreased in the exhaustive exercise group. The ANP electron-dense granules and the quantity and volume of mitochondria increased in moderate and high-intensity exercise group. The ANP electron dense granules decreased and the mitochondria tumefied in the exhaustive exercise group. The changes of plasma ANP have a tendency of increasing gradually with increase in exercise intensity. Moderate and high-intensity exercise increases ANP synthesis and storage in cardiomyocytes and induces adaptive changes in the ultrastructure of cardiomyocytes. The decrease of ANP immunoreactivity in cardiomyocytes after exhaustive exercise is probably the result of massive depletion and induces damaging changes in the ultrastructure of cardiomyocytes.

Left atrial remodelling contributes to the progression of asymptomatic left ventricular systolic dysfunction to chronic symptomatic heart failure

Systolic heart failure (HF) is a progressive disorder that often begins with asymptomatic left ventricular (LV) systolic dysfunction and culminates in symptoms from fluid overload and poor end-organ perfusion. The progression to symptomatic HF is accompanied by marked activation of neurohormonal and cytokine systems, as well as a series of adaptive LV anatomical and functional changes, collectively referred to as LV remodelling. However, the mechanisms underlying symptom appearance have not been delineated and the weight of experimental and clinical evidence suggests that the development of symptomatic HF occurs independently of the haemodynamic status of the patient. The left atrium is a muscular chamber strategically located between the left ventricle and the pulmonary circulation with important mechanical function (modulation of LV filling), which is closely coupled with its endocrine (atrial natriuretic peptide synthesis and secretion) and regulatory (contribution to the control of sympathetic activity and vasopressin release) functions. In this narrative review we provide evidence supporting the concept that left atrial dilation and systolic dysfunction (left atrial remodelling) contributes to the progression of asymptomatic LV dysfunction to chronic symptomatic systolic HF as it is a prerequisite for the development of the pulmonary congestion and marked neuronhormoral activity that characterize the symptomatic state.

Imidazoline receptors in the heart: a novel target and a novel mechanism of action that involves atrial natriuretic peptides.

Chronic stimulation of sympathetic nervous activity contributes to the development and maintenance of hypertension, leading to left ventricular hypertrophy (LVH), arrhythmias and cardiac death. Moxonidine, an imidazoline antihypertensive compound that preferentially activates imidazoline receptors in brainstem rostroventrolateral medulla, suppresses sympathetic activation and reverses LVH. We have identified imidazoline receptors in the heart atria and ventricles, and shown that atrial I1-receptors are up-regulated in spontaneously hypertensive rats (SHR), and ventricular I1-receptors are up-regulated in hamster and human heart failure. Furthermore, cardiac I1-receptor binding decreased after chronic in vivo exposure to moxonidine. These studies implied that cardiac I1-receptors are involved in cardiovascular regulation. The presence of I1-receptors in the heart, the primary site of production of natriuretic peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), cardiac hormones implicated in blood pressure control and cardioprotection, led us to propose that ANP may be involved in the actions of moxonidine. In fact, acute iv administration of moxonidine (50 to 150 microg/rat) dose-dependently decreased blood pressure, stimulated diuresis and natriuresis and increased plasma ANP and its second messenger, cGMP. Chronic SHR treatment with moxonidine (0, 60 and 120 microg kg(-1) h(-1), sc for 4 weeks) dose-dependently decreased blood pressure, resulted in reversal of LVH and decreased ventricular interleukin 1beta concentration after 4 weeks of treatment. These effects were associated with a further increase in already elevated ANP and BNP synthesis and release (after 1 week), and normalization by 4 weeks. In conclusion, cardiac imidazoline receptors and natriuretic peptides may be involved in the acute and chronic effects of moxonidine.