Brain Natriuretic Polypeptide Research Articles

Baicalin inhibits pressure overload-induced cardiac hypertrophy by regulating the SIRT3-dependent signaling pathway

BackgroundThe conserved sirtuin protein sirtuin 3 (SIRT3) is a vital protective protein for cardiac hypertrophy. Inhibition of SIRT3 accelerated the development of heart hypertrophy. On the other hand, myocardial hypertrophy was prevented by overexpressing SIRT3. SIRT3 has been proposed as a potential therapeutic target for managing or averting heart hypertrophy. Baicalin, a flavonoid extracted from the Scutellaria baicalensis plant, has anti-cardiovascular properties, including protection against cardiac hypertrophy. However, the molecular mechanism of the anti-hypertrophic effect of baicalin is not well known. PurposeIn this study, we aim to investigate the effect of baicalin on cardiac hypertrophy and explored its underlying molecular mechanisms. Study-design/methodsAbdominal aortic constriction (AAC)-induced mouse cardiac hypertrophy and angiotensin II (Ang II)-induced cardiomyocyte hypertrophy models were established. After baicalin treatment, cardiac hypertrophy was monitored by detecting the expression of hypertrophic genes and cell surface area. Echocardiogram was performed to check the heart function in vivo. Moreover, the protein expression of the SIRT3-dependent pathway was detected by Western blotting. ResultsIn this work, we demonstrated that baicalin might suppress the cell surface area and the expression of the Ang II -induced myosin heavy chain β (β-MHC), brain natriuretic polypeptide (BNP), and atrial natriuretic factor (ANF). Additionally, it reduced the AAC rats' hypertrophic impact. We also found that baicalin prevents cardiac hypertrophy by regulating SIRT3/LKB1/AMPK signaling pathway. Moreover, we showed that baicalin upregulated the SIRT3 protein expression by inhibiting proteasome and by the activation of 20 S proteasome subunit beta type-5 (PSMB5). ConclusionThese results offer the first proof that baicalin inhibits cardiac hypertrophy due to its effect on the SIRT3-dependent signaling pathway, indicating its potential for treating cardiac hypertrophy and heart failure. The present study provides a preliminary experimental basis for the clinical application of baicalin and baicalin-like compounds.

Impact of Pre-Revascularization and Post-Revascularization Cardiac Arrest on Survival Prognosis in Patients With Acute Myocardial Infarction and Following Emergency Percutaneous Coronary Intervention

Objectives: To evaluate the effects of occurrence and timing of sudden cardiac arrest (SCA) on survival in patients with acute myocardial infarction (AMI) who underwent emergency percutaneous coronary intervention (PCI).Methods: We analyzed 1,956 consecutive patients with AMI with emergency PCI from 2014 to 2018. Patients with cardiac arrest events were identified, and their medical records were reviewed.Results: Patients were divided into non-cardiac arrest group (NCA group, n = 1,724), pre-revascularization cardiac arrest (PRCA group, n = 175), and post-revascularization SCA (POCA group, n = 57) according to SCA timing. Compared to NCA group, PRCA group and POCA group presented with higher brain natriuretic polypeptide (BNP), more often Killip class 3/4, atrial fibrillation, and less often completed recovery of coronary artery perfusion (all p < 0.05). Both patients with PRCA and POCA showed increased 30-day all-cause mortality when compared to patients with NCA (8.0 and 70.2% vs. 2.9%, both p < 0.001). However, when compared to patients with NCA, patients with PRCA did not lead to higher mortality during long-term follow-up (median time 917 days) (16.3 vs. 18.6%, p = 0.441), whereas patients with POCA were associated with increased all-cause mortality (36.3 vs. 18.6%, p < 0.001). Multivariate analysis identified Killip class 3/4, atrial fibrillation, high maximum MB isoenzyme of creatine kianse, and high creatinine as predictive factors for POCA. In Cox regression analysis, POCA was found as a strong mortality-increase predictor (HR, 8.87; 95% CI, 2.26–34.72; p = 0.002) for long-term all-cause death.Conclusions: POCA appeared to be a strong life-threatening factor for 30-day and long-term all-cause mortality among patients with AMI who admitted alive and underwent emergency PCI. However, PRCA experience did not lead to a poorer long-term survival in patients with AMI surviving the first 30 days.

Selection of AVP-Shortage Patients as Candidates for Low-Dose Oral Desmopressin Administration.

ObjectiveWe herein attempted to select male patients with an elevated nocturnal urinary frequency possibly due to a shortage of AVP. These patients may be good candidates for low-dose oral desmopressin administration.Patients and MethodsSerum and spot urine osmolality, electrolytes, serum creatinine, casual blood glucose, plasma brain natriuretic polypeptide (BNP), and plasma AVP were measured at the same time in 97 elderly male patients with urinary symptoms under free water drinking.ResultsA binary plot of plasma AVP and serum osmolality indicated a region at which patients had relatively lower AVP considering higher serum osmolality. It was tentatively named the desmopressin region. Twenty out of 97 (20.6%) patients were in the desmopressin region. Daily urine output did not exceed 3 L in any patient. Urine osmolality was slightly lower in patients in the desmopressin region. No significant differences were observed in urine volume, urinary frequency, or urination questionnaire scores between both groups.ConclusionAVP-shortage patients may be selected for treatment with oral desmopressin based on measurements of serum osmolality and plasma AVP.

Citri Reticulatae Pericarpium protects against isoproterenol-induced chronic heart failure via activation of PPARγ.

BackgroundAccumulated clinical trials and animal studies showed that Qiliqiangxin (QLQX), a traditional Chinese medicine formula containing extracts of 11 herbs, exerts beneficial effects on chronic heart failure (HF). Citri Reticulatae Pericarpium (CRP), one herbal medicine in QLQX, has been widely used in treatment against digestive, respiratory and cardiovascular diseases (CVDs) in China. However, the cardiac protective effects and mechanisms of CRP are still unclear.MethodsThe effects of CRP were investigated in isoproterenol (ISO)-induced chronic HF mice model and neonatal rat ventricular cardiomyocytes (NRVMs) treated with ISO. Echocardiography was used to determine cardiac function. Hematoxylin-eosin (HE) staining and α-actinin immunofluorescent staining were used to measure cardiomyocyte size. Cardiac fibrosis was evaluated by Masson’s trichrome staining. The expression of atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) were determined by quantitative real time PCR (qRT-PCR). Western blot was applied to examine the expression of peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α (PGC-1α), fibrosis-related and apoptosis-related proteins.ResultsWe found that CRP could significantly attenuate ISO-induced cardiac dysfunction, inhibit cardiac pathological hypertrophy and alleviate myocardial fibrosis and apoptosis. Mechanistically, the downregulation of PPARγ and PGC-1α in ISO-injected mice hearts and ISO-treated NRVMs could be reversed by CRP treatment. The beneficial effects of CRP against ISO-induced HF were abolished by PPARγ inhibitor (T0070907), suggesting that CRP-mediated PPARγ upregulation was essential for the preventive effect of CRP on ISO-induced cardiac dysfunction.ConclusionsIn conclusion, our study demonstrated that CRP attenuates ISO-induced cardiac remodeling via PPARγ activation, which represents a new application for CRP in the prevention of chronic HF.

Kallistatin alleviates heart failure in rats by inhibiting myocardial inflammation and apoptosis via regulating sirt1.

Heart failure (HF) is the loss of myocardial structure and function caused by various congenital or acquired heart diseases. This study explored the new target of treatment of HF by investigating the effect of Kallistatin (KS) on inflammation and apoptosis of myocardial tissue in HF rats. We used doxorubicin to induce rat HF, and determined the success rate of modeling by detecting changes in rat heart weight and body weight, cardiac function and histology. We used two different doses (1 mg/kg, 2 mg/kg) of KS intraperitoneally injected rats and detected changes in inflammation and apoptosis of rat myocardial tissue by enzyme-linked immunosorbent assay (ELISA), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining. Changes in the expression of sirt1 were also detected. In addition, we cultured rat myocardial cell line, H9c2 cells, and used siRNA-sirt1 to inhibit sirt1 in H9c2 cells to clarify the mechanism of KS regulating myocardial cells. The body weight of HF rats treated with KS decreased while the heart weight increased. KS has also been found to reduce the concentration of brain natriuretic polypeptide (BNP) in rat serum. The results of echocardiography showed that KS effectively relieved the cardiac function of HF rats. Inflammatory factors (interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α) and pro-apoptotic molecules (caspase3/9 and Bax) in the serum and myocardial tissue of rats treated with KS were also significantly reduced. The inhibition of sirt1 in H9c2 cells significantly reduced the anti-apoptotic effect of KS on H9c2 cells. KS reduces the inflammation and apoptosis of myocardial tissue in HF rats by promoting the expression of sirt1, thereby alleviating HF-induced myocardial injury.

Taurine attenuates isoproterenol-induced H9c2 cardiomyocytes hypertrophy by improving antioxidative ability and inhibiting calpain-1-mediated apoptosis.

Pathological cardiac hypertrophy is ultimately accompanied by cardiomyocyte apoptosis. Apoptosis mainly related to calpain-1-mediated apoptotic pathways. Studies had proved that taurine can maintain heart health through antioxidation and antiapoptotic functions, but the effect of taurine on cardiachypertrophy is still unclear. This study aimed to determine whether taurine could inhibit calpain-1-mediated mitochondria-dependent apoptotic pathways in isoproterenol (ISO)-induced hypertrophic cardiomyocytes. We found that taurine could inhibit the increase in cell surface area and reduce the protein expression levels of the hypertrophic markers atrial natriuretic peptide, brain natriuretic polypeptide, and β-myosin heavy chain. Taurine also reduced ROS, intracellular Ca2+ overload and mitochondrial membrane potential. Moreover, taurine inhibited cardiomyocyte apoptosis by decreasing the protein expression of calpain-1, Bax, t-Bid, cytosolic cytochrome c, Apaf-1, cleaved caspase-9 and cleaved caspase-3 and by enhancing calpastatin and Bcl-2 protein expression. Calpain-1 small interfering RNA transfection results showed similar antiapoptotic effects as the taurine prevention group. However, compared with the two treatments, taurine inhibited the expression of cleaved caspase-9 more significantly. Therefore, we believe that taurine prevents ISO-induced H9c2 cardiomyocyte hypertrophy by inhibiting oxidative stress, intracellular Ca2+ overload, the calpain-1-mediated mitochondria-dependent apoptotic pathway and cleaved caspase-9 levels.

SIRT6 Suppresses NFATc4 Expression and Activation in Cardiomyocyte Hypertrophy.

NFATc4, a member from the Nuclear Factor of Activated T cells (NFATs) transcription factor family, plays a pivotal role in the development of cardiac hypertrophy. NFATc4 is dephosphorylated by calcineurin and translocated from the cytoplasm to the nucleus to regulate the expression of hypertrophic genes, like brain natriuretic polypeptide (BNP). The present study identified SIRT6, an important subtype of NAD+ dependent class III histone deacetylase, to be a negative regulator of NFATc4 in cardiomyocyte hypertrophy. In phenylephrine (PE)-induced hypertrophic cardiomyocyte model, overexpression of SIRT6 by adenovirus infection or by plasmid transfection repressed the protein and mRNA expressions of NFATc4, elevated its phosphorylation level, prevented its nuclear accumulation, subsequently suppressed its transcriptional activity and downregulated its target gene BNP. By contrast, mutant of SIRT6 without deacetylase activity (H133Y) did not demonstrate these effects, suggesting that the inhibitory effect of SIRT6 on NFATc4 was dependent on its deacetylase activity. Moreover, the effect of SIRT6 overexpression on repressing BNP expression was reversed by NFATc4 replenishment, whereas the effect of SIRT6 deficiency on upregulating BNP was recovered by NFATc4 silencing. Mechanistically, interactions between SIRT6 and NFATc4 might possibly facilitate the deacetylation of NFATc4 by SIRT6, thereby preventing the activation of NFATc4. In conclusion, the present study reveals that SIRT6 suppresses the expression and activation of NFATc4. These findings provide more evidences of the anti-hypertrophic effect of SIRT6 and suggest SIRT6 as a potential therapeutic target for cardiac hypertrophy.

Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto: Atrial Fibrillation Suppression Trial (SILK study)

BackgroundExperimental studies suggest that angiotensin II-receptor blockers can influence atrial remodeling and may prevent atrial fibrillation (AF). Therefore, we hypothesized that irbesartan may prevent the recurrence of AF following either catheter ablation or electrical cardioversion of AF. MethodsStudy on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto (SILK study) is a prospective, multicenter, randomized, and open-label comparative evaluation of the effects of irbesartan and amlodipine on AF recurrence in hypertensive patients with AF who are scheduled to undergo catheter ablation or electrical cardioversion of AF. The primary end point was either AF or atrial tachycardia (AT) recurrence. AF/AT recurrence was evaluated for 6 months using 24-h Holter electrocardiogram and portable electrocardiogram. The secondary endpoints included the change in blood pressure, the interval from the procedure to the first AF/AT recurrence, cardiovascular events, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), and changes in the biomarkers [brain natriuretic polypeptide (BNP), high-sensitivity C-reactive protein (hs-CRP), urinary albumin/creatinine]. ResultsThe study enrolled 98 patients (irbesartan; n=47, amlodipine; n=51). The recurrence of AF/AT was observed in 8 patients (17.0%) in the irbesartan group and in 10 patients (19.6%) in the amlodipine group. There was no significant difference in the AF/AT recurrence between the irbesartan and amlodipine groups. Blood pressure decreased similarly in both groups. There were no significant differences between the two groups as regards to the interval from the procedure to the first AF/AT recurrence, occurrence of cardiovascular events, changes in LAD and LVEF. BNP and urinary albumin/creatinine significantly decreased similarly in both groups, but no significant difference was found in hs-CRP between the two groups. ConclusionsIn hypertensive patients with AF, treatment with irbesartan did not have any advantage over amlodipine in the reduction of AF/AT recurrence after catheter ablation or electrical cardioversion.

The orphan receptor NOR1 participates in isoprenaline-induced cardiac hypertrophy by regulating PARP-1.

The orphan nuclear receptor NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, and is involved in glucose and fat metabolism. However, its potential contribution to cardiovascular diseases remains to be assessed. Here, the roles of NOR1 in cardiac hypertrophy induced by isoprenaline and the underlying molecular mechanisms were investigated. NOR1 was expressed in cardiomyocytes treated with isoprenaline. After NOR1 overexpression or knockdown in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA of hypertrophic biomarkers. Interactions between NOR1 and PARP-1 were investigated by co-immunoprecipitation. NOR1 expression and PARP-1 activity were measured in rats with cardiac hypertrophy induced by isoprenaline. Treatment with isoprenaline significantly up-regulated NOR1 expression and PARP-1 activity both in vivo and in vitro. Specific gene silencing of NOR1 attenuated isoprenaline-induced cardiomyocyte hypertrophy, whereas NOR1 overexpression exacerbated cardiac hypertrophy. We identified a physical interaction between NOR1 and PARP-1, which was enhanced by NOR1 transfection and thereby led to PARP-1 activation. Overexpression of NOR1, but not C293Y, a NOR1 mutant lacking the PARP-1 binding activity, increased cellular surface area and the mRNA levels of atrial natriuretic factor and brain natriuretic polypeptide, effects blocked by the PARP-1 inhibitor 3-aminobenzamide or siRNA for PARP-1. This is the first evidence that NOR1 was involved in isoprenaline-induced cardiac hypertrophy. The pro-hypertrophic effect of NOR1 can be partly attributed to its regulation of PARP-1 enzymic activity.

EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes, by Activating AMPK-Dependent Pathway.

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

Effect of anemia correction to the modestly high hemoglobin level in patients with chronic kidney disease on left ventricular hypertrophy

Background and purposeTo assess effects of long-term anemia management on left ventricular hypertrophy in patients with chronic kidney disease (CKD) not on dialysis, we performed secondary outcome analyses of a randomized controlled study that evaluated effects of anemia management with erythropoiesis stimulating agents in this population. Methods and subjectsSubjects [hemoglobin (Hb)<10.0g/dL, 2.0≤serum creatinine<6.0mg/dL] were randomized either to high Hb (11.0≤target Hb≤13.0g/dL with darbepoetin alfa), or to low Hb group (9.0≤target Hb≤11.0g/dL with recombinant human erythropoietin), and followed up to 48 weeks. Data from echocardiographic evaluation and values of neurohumoral factors associated with heart failure were assessed in subjects whose data were evaluable both at the baseline and at the end point. ResultsThe high Hb group achieved target range Hb levels (12.1±1.1g/dL, at 32 weeks, N=111), which was significantly higher (p<0.001) than the low Hb group (N=95). Though blood pressure and renal function changes were similar between the groups, left ventricular diastolic dimension was significantly decreased only in the high Hb group (p<0.001), and the change in left ventricular mass index (LVMI) correlated coarsely but significantly with the achieved Hb levels (r=0.147, p=0.032). The higher Hb levels were associated with greater reduction in LVMI and left ventricular wall thickness, and the lower Hb levels with the greater increase in human arterial- or brain natriuretic polypeptide levels. ConclusionsAnemia correction targeting modestly higher Hb levels better preserves cardiac function in CKD patients not on dialysis.

Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level

Diabetic cardiomyopathy, structurally characterized by cardiomyocyte hypertrophy and increased extracellular matrix (ECM) protein deposition, eventually leads to heart failure. We investigated the role of transcriptional coactivator p300 and its interaction with myocyte enhancer factor 2 (MEF2) in diabetes-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed to variable levels of glucose. Cardiomyocytes were analyzed with respect to their size. mRNA expression of p300, MEF2A, MEF2C, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), angiotensinogen (ANG), cAMP-responsive element binding protein-binding protein (CBP), and protein analysis of MEF2 were done with or without p300 blockade. We investigated the hearts of STZ-induced diabetic rats and compared them with age- and sex-matched controls after 1 and 4 mo of followup with or without treatment with p300 blocker curcumin. The results were that cardiomyocytes, exposed to 25 mM glucose for 48 h, showed cellular hypertrophy and augmented mRNA expression of ANP, BNP, and ANG, molecular markers of cardiac hypertrophy. Glucose caused a duration-dependent increase of mRNA and protein expression in MEF2A and MEF2C and transcriptional coactivator p300. Curcumin, a p300 blocker, and p300 siRNA prevented these abnormalities. Similarly, ANP, BNP, and ANG mRNA expression was significantly higher in the hearts of diabetic rats compared with the controls, in association with increased p300, MEF2A, and MEF2C expression. Treatment with p300 blocker curcumin prevented diabetes-induced upregulation of these transcripts. We concluded that data from these studies demonstrate a novel glucose-induced epigenetic mechanism regulating gene expression and cardiomyocyte hypertrophy in diabetes.

Evaluation of atrial and brain natriuretic polypeptides in association with angiotensin-converting enzyme gene polymorphism in Japanese non-diabetic hemodialysis patients

Insertion (I)/deletion (D) polymorphisms in the angiotensin-converting enzyme (ACE) gene have the potential to serve as a marker for an increased risk of cardiovascular events. Increased plasma levels of human atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) are important indexes of cardiac function. The aim of this study was to examine possible relationships between I/D polymorphisms and the myocardial release of ANP and BNP in Japanese hemodialysis (HD) patients (n=131). We studied 131 non-diabetic hemodialysis patients. The genotype of ACE gene was determined by polymerase chain reaction with a set of specific timers. ANP and BNP levels were measured before HD. The plasma levels of ANP and BNP were significantly lower in the DD genotype group compared to those in the II group. Corresponding levels in the ID genotype group were intermediate between those in the DD and II groups. ACE polymorphism was associated with neither ejection fraction nor left ventricular mass/height index (LVMI), as evidenced by echocardiographic findings (n=107). Plasma levels of ANP were significantly correlated with left atrial diameter (LAD) in patients as a whole, but this correlation was only observed in the II genotype group, and not in the DD or ID groups. Plasma levels of BNP were significantly correlated with LAD, left ventricular end systolic diameter and LVMI in patients as a whole, but these correlations were seen only in the II genotype group. The results suggest that the plasma levels of these natriuretic peptides should be evaluated on the basis of ACE polymorphism for assessing cardiac diseases due to volume overload in Japanese HD patients.

Anemia is Associated with Enhanced Secretion of Brain Natriuretic Polypeptide and Increased Ventricular Mass in Diastolic Heart Failure

Anemia is Associated with Enhanced Secretion of Brain Natriuretic Polypeptide and Increased Ventricular Mass in Diastolic Heart Failure

Prognostic significance of elevated plasma brain natriuretic polypeptide in patients with chronic renal failure treated with hemodialysis

Prognostic significance of elevated plasma brain natriuretic polypeptide in patients with chronic renal failure treated with hemodialysis

Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation

Background: Plasma brain natriuretic polypeptide (BNP) levels have been used as biochemical markers of systolic left ventricular (LV) dysfunction. Although in vitro studies have shown the existence of BNP messenger RNA in the atria, the main production site of BNP is believed to be the ventricle. The hypothesis that the atrium could be a source of BNP was examined in patients with lone atrial fibrillation (AF), the most common type of sustained arrhythmia. Methods and Results: We studied 16 controls and 21 patients with lone AF. Plasma samples for BNP were selectively and serially obtained from the aorta, anterior interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic polypeptide (ANP) levels were also measured to determine whether the CS samples contained significant amounts of atrial venous drainage. Of the 3 sample locations, the CS had the greatest ANP levels, confirming transcatheter sampling position accuracy. BNP levels were significantly greater in the CS than AIV in the patients with AF (279±226 v 126±97 pg/mL; P < .01). Consequently, plasma BNP levels were also greater in the patients with AF than controls (103±90 v 5±2 pg/mL; P < .001). LV ejection fraction was significantly less in patients with AF than control patients. Atrial production of BNP decreased significantly after successful DC cardioversion of AF in the 5 restudied patients (182±139 v 59±64 pg/mL; P < .05). Conclusion: The data suggest that AF is a condition in which BNP is produced in the atrium itself.

Atrium as a source of brain natriuretic polypeptide in patients with atrial fibrillation

<h2>Abstract</h2> <b>Background:</b> Plasma brain natriuretic polypeptide (BNP) levels have been used as biochemical markers of systolic left ventricular (LV) dysfunction. Although in vitro studies have shown the existence of BNP messenger RNA in the atria, the main production site of BNP is believed to be the ventricle. The hypothesis that the atrium could be a source of BNP was examined in patients with lone atrial fibrillation (AF), the most common type of sustained arrhythmia. <b>Methods and Results:</b> We studied 16 controls and 21 patients with lone AF. Plasma samples for BNP were selectively and serially obtained from the aorta, anterior interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic polypeptide (ANP) levels were also measured to determine whether the CS samples contained significant amounts of atrial venous drainage. Of the 3 sample locations, the CS had the greatest ANP levels, confirming transcatheter sampling position accuracy. BNP levels were significantly greater in the CS than AIV in the patients with AF (279±226 <i>v</i> 126±97 pg/mL; <i>P</i> < .01). Consequently, plasma BNP levels were also greater in the patients with AF than controls (103±90 <i>v</i> 5±2 pg/mL; <i>P</i> < .001). LV ejection fraction was significantly less in patients with AF than control patients. Atrial production of BNP decreased significantly after successful DC cardioversion of AF in the 5 restudied patients (182±139 <i>v</i> 59±64 pg/mL; <i>P</i> < .05). <b>Conclusion:</b> The data suggest that AF is a condition in which BNP is produced in the atrium itself.

Inhibition by brain natriuretic polypeptide (BNP) on neurons in the supraoptic nucleus and the region of the anteroventral third ventricle

Inhibition by brain natriuretic polypeptide (BNP) on neurons in the supraoptic nucleus and the region of the anteroventral third ventricle

Inhibition by brain natriuretic polypeptide (BNP) on neurons in the supraoptic nucleus and the region of the anteroventral third ventricle : Shigeki Yamamoto, Kiyotoshi Inenaga, Masanori Kasai, Hiroshi Yamashita, Dept. Physiol., Univ. Occup. & Environ. Health, Sch. of Med., Yahatanishi-ku, Kitakyushu 807, Japan

Inhibition by brain natriuretic polypeptide (BNP) on neurons in the supraoptic nucleus and the region of the anteroventral third ventricle : Shigeki Yamamoto, Kiyotoshi Inenaga, Masanori Kasai, Hiroshi Yamashita, Dept. Physiol., Univ. Occup. & Environ. Health, Sch. of Med., Yahatanishi-ku, Kitakyushu 807, Japan

The heart is the center of a new endocrine, paracrine, and neuroendocrine system.

This review indicates that the heart is a polypeptide-producing organ which should be classified among the traditional endocrine tissues. Cardiac hormones have only been known for a few years, the discovery of their endocrine functions, however, occurred in the 1950ies when Gauer, Henry and Kisch observed specific physiological and morphological features of the heart atria indicative of an endocrine activity. Because of their basic effects many target organs involved in the regulation of body fluid pressure and composition are related to this endocrine organ located in the atrial appendages of the heart. The compact endocrine portion of the heart is built up by myoendocrine cells which form the functional endocrine units and produce a variety of polypeptide hormones called cardiodilatin (CDD) or atrial natriuretic polypeptide (ANP), which belong to one family. Also, co-storage of a partially homologous regulatory polypeptide called brain natriuretic polypeptide (BNP) occurs, as has been determined by immunohistochemistry and radioimmunoassay. CDD and/or BNP are found in numerous organs where they exert paracrine and neurocrine functions, e.g., in the brain, peripheral nervous system, kidney, and adrenal medulla. In these organs, a differential post-translational processing of cardiac polypeptides is observed, resulting in different functional activities according to discriminating receptor interactions and degrading metabolism. Some of the extra-auricular sites of synthesis and storage of CDD-like peptides are briefly mentioned. In summary the heart constitutes the center of a multilocal and multifunctional system of specific cardiac polypeptides of endocrine, paraneuronal, and neuronal character.