The ratio of N-terminal pro-B-type natriuretic peptide to troponin I for differentiating acute coronary syndrome.

INTRODUCTION: It is difficult to differentiate whether coronary or non-coronary causes in patients with elevated troponin I (TnI) in emergency department (ED). The aim of this study was to develop a clinical decision tool for differentiating a coronary cause in the patients with elevated TnI. METHODS: This was a retrospective observational study that enrolled consecutive ED patients. Patients were included in the study if they were ≥16 years of age, had admitted through ED with a medical illness, and TnI levels at initial evaluation in the ED were ≥0.2 ng/mL. Patients diagnosed with ST elevation myocardial infarction or congestive heart failure were excluded. Coronary angiography, electrocardiogram, laboratory results, echocardiography, and clinical characteristics were analyzed. RESULTS: Among the included 1441 patients, 603 and 838 patients were categorized into an acute coronary syndrome (ACS) group and non-acute coronary syndrome (non-ACS) group, respectively. The ratio of N-terminal pro-Btype natriuretic peptide (NT-proBNP) to TnI was significantly higher in the non-ACS group compared to the ACS group. The AUC of NT-proBNP/TnI (0.805, 95% CI, 0.784-0.826) was significantly superior to that of NT-proBNP/creatinine kinase-MB, TnI, and NT-proBNP. The patients of the non-ACS group with high levels of TnI and BNP showed more critically ill manifestation at the time of presentation and higher mortality. CONCLUSION: NT-proBNP/TnI may help to distinguish medical patients with elevated TnI whether the elevated TnIs were caused from ACSs or from conditions other than ACS.

Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus, cytoplasm, endothelium, and fibroblasts of human cancers.

Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) synthesized by the same gene decrease within 24 hours up to 97% the number of human breast, colon, pancreatic, and prostate adenocarcinoma cells as well as human small-cell and squamous carcinomas of the lung cells. These peptide hormones completely inhibit the growth of human pancreatic adenocarcinomas growing in athymic mice. Immunocytochemical investigations have revealed that LANP, vessel dilator, kaliuretic peptide and ANP localize to the nucleus and cytoplasm of human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer mediated by the intracellular messenger cyclic GMP. These peptide hormones also localize to the endothelium of capillaries and fibroblasts within these cancers. These are the first growth-inhibiting peptide hormones ever demonstrated to localize to the nucleus. Their ability to decrease the activation of growth promoting substances such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear Factor Kappa Beta (NFkappaB) suggests that in addition to inhibiting DNA synthesis their ability to decrease the activation of growth promoting substances helps to mediate their ability to inhibit the growth of human cancers.

Comparative analysis of the natriuretic peptide precursor gene cluster in vertebrates reveals loss of ANF and retention of CNP-3 in chicken.

We identified and characterized the chicken natriuretic peptide precursor gene cluster and found its organization to be highly conserved compared with the mammalian Nppb-Nppa cluster. However, phylogenetic analysis indicated that the putative chicken natriuretic peptide precursor genes are the homologues of CNP-3 and Nppb, respectively. Comparative expression analysis revealed that, in human, mouse, and rat hearts, Nppb is a novel marker for the differentiating working myocardium. Its expression pattern is strikingly similar to that of Nppa before birth, and diverges only after birth. In contrast, whereas the chicken Nppb gene expression profile resembled that of mammalian Nppb, the CNP-3 gene showed very limited expression in the heart, not resembling the pattern of either Nppa or Nppb. These results show that, in chicken, the Nppa gene has been lost from the natriuretic peptide precursor gene cluster, whereas the CNP-3 gene has been retained.

B and C types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus.

We previously reported that atrial natriuretic factor (ANF) regulates catecholamine metabolism in the central nervous system. ANF, B and C types natriuretic peptides (BNP and CNP) also play a regulatory role in body fluid homeostasis, cardiovascular activity and hormonal and neuro-hormonal secretions. The aim of the present work was to investigate BNP and CNP effects on the uptake and release of norepinephrine (NE) in rat hypothalamic slices incubated in vitro. Results showed that BNP (100 nM) and CNP (1, 10 and 100 nM) enhanced total and neuronal [3H]NE uptake but did not modify non-neuronal uptake. BNP (100 nM) and CNP (1 nM) caused a rapid increase in NE uptake (1 min), which was sustained for 60 min. BNP (100 nM) did not modify the intracellular distribution of NE; however, 1 nM CNP increased the granular store and decreased the cytosolic pool of NE. BNP (100 nM) and CNP (1, 10 and 100 nM), diminished spontaneous NE release. In addition, BNP (1, 10, 100 nM) and CNP (1, 10 and 100 pM, as well as 1, 10 and 100 nM) reduced NE output induced by 25 mM KCl. These results suggest that BNP and CNP may be involved in the regulation of several central as well as peripheral physiological functions through the modulation of noradrenergic neurotransmission at the presynaptic neuronal level. Present results provide evidence to consider CNP as the brain natriuretic peptide since physiological concentrations of this peptide (pM) diminished NE evoked release.

Efecto del estrés sobre la formación de GMPc inducida por el péptido natriurético auricular en el núcleo paraventricular de la rata / Effect of the stress on the formation of GMPc inducen by the peptide natriuretic auricular in the nucleous of the rats

Se ha descrito en el cerebro un sistema peptidérgico complejo, relacionado con el balance hidrotermial y el control neuroendocrino. Para este sistema se ha descrito la existencia de tres ligandos endógenos (PNA, BNP, y CNP) y al menos tres subtipos de receptores, dos de ellos, GC-A y GC-B, acoplados a la guanililciclasa (GC), ambos pertenecientes al grupo denominado R1, y el tercero, el receptor R2, no acoplado a la GC y considerando un receptor metabólico. Al igual que en la periferia, los efectos de estos péptidos estan mediados por receptores de membrana acoplados a la GC, con la consecuente producción de GMPc. Estos receptores, y posiblemente la actividad GC estimulable por el PNA, son regulables en forma inversa por el péptido local o circulante. Ciertas manipulaciones del eje hipotálamo-hipófisis-glándula suprarrenal (HHGS) inducen alteraciones en los niveles locales y circulantes de PNA en áreas localizadas del cerebro como el núcleo paraventricular (NPV). Evaluamos si la alteración en los receptores para el PNA en el NPV, está asociada a modificaciones en la capacidad de producción de GMPc inducida por el PNA. Para ello, utilizamos dos modelos experimentales donde ocurre una intensa activación del eje HHGS. el estrés por estímulo eléctrico plantar (EEP) y el estrés por inmobilización forzada (IMO). En ambos modelos se produce un incremento de la máxima capacidad de formación de GMPc inducida por el PNA. Estos resultados indican un papel del PNA en la función regulatoria del NVP y sugieren que los receptores R1 para el PNA son suceptibles a ser modulados durante el estrés

Organization of the gene for iso-rANP, a rat B-type natriuretic peptide.

Using the polymerase chain reaction and oligonucleotide primers constructed from knowledge of the cDNA sequence we have sequenced the gene for iso-rANP, a peptide of the B-type of atrial natriuretic peptides. The overall organization of the rat iso-ANP gene is the same as that of ANP and BNP consisting of three exons and two introns at relatively similar positions. Iso-rANP and it's gene are more closely related to BNPs than ANP and yet there are significant differences at both the protein and DNA levels. Our results suggest that iso-rANP and BNP are distinct members of the same sub-family (B-type natriuretic peptides) within the family of natriuretic peptide genes.

[Contents and molecular forms of human atrial natriuretic peptide in right and left auricle in patients with heart disease].

Contents and molecular forms of human atrial natriuretic peptide (hANP) in right and left auricle were analyzed by reverse phase high liquid chromatography (RP-HPLC), coupled with radioimmunoassay for hANP. Analyses were done with auricles taken from 4 autopsied cases without heart disease, and 13 patients with heart disease. Both right and left auricular hANP contents in patients with heart disease were higher than those obtained at autopsy. In patients with mitral stenosis (MS) or mitral regurgitation (MR) who have left atrial pressure and/or volume overload, hANP contents in left auricle were higher than those in right auricle. In addition, three types of molecular forms of hANP, (gamma) type, (alpha, beta, gamma) type, (beta, gamma) type, were observed in both right and left atrium. In patients with MS or MR, (beta, gamma) type or (alpha, beta, gamma) type which have beta-hANP immunoreactivity were observed in 8 out of 9 in patients in left auricle, however, in 4 out of 9 patients in right auricle. Our results suggested that the difference of contents and molecular forms of hANP may reflect the pathophysiological role in heart diseases.