Meta-analysis about Atrial Natriuretic Peptide (ANP)

Among the topics studied in physiology and aging, a hormone has been drawing attention from the scientificcommunity: the Atrial Natriuretic Peptide (ANP). The ANP, which is produced by the cardiac atria, hasdemonstrated decisive action in endocrine mechanisms of action inhibiting sodium reabsorption in nephrons,revealing a direct influence on physiological mechanisms linked to aging and chronic stress.The overall objectiveof this study was to assess and analyze scientific literature on the ANP in the Pubmed database from 2010 to2012. 30 articles were collected, verifying authorship and gender division of species, instruments and typesof research. The results showed that the research of multiple authorship appeared mostly with 99.1%, being51.8% of male authorship, 17.9% of female authorship and 29.5% of publications not identified. Researchwith only one author appears with 0.8% in total. As the types of species used, it was observed 50.3% of theworks with humans, 40% with animals and 6.7% mixed (animal / human). As to the instruments used, thebiochemical markers were the ones that stood out, with 30%, followed by label arterial pressure with 12, 2%,drugs, with 11.1% and microscopic studies with 10%. In the typology of research, biochemical research appearsfirst, with 33.3%, followed by research morphophysiological/biochemical research, with 30%, Physiological/ biochemical, with 26.7%, Physiological with 6.7% and Morphophysiological with 3.3%. We can concludethat the publications about the hormone ANP are still little explored when the focus is aging. In the analyzedpublications, there is important information about the physiological and biochemical role of ANP as well ason their molecular composition.

Peptídeos natriuréticos / Natriuretic peptides

Os peptídeos natriuréticos são biomarcadores liberados pelo coração e endotélio vascular, que têm importante função na regulação da homeostase. Participam da fisiologia renal e cardíaca, bem como possuem papel fisiopatológico na insuficiência cardíaca, na hipertensão e na doença renal. Dentre os peptídeos natriuréticos atrial (ANP) e o peptídeo natriurético cerebral (BNP). Atualmente, diversas pesquisas demonstram sua importancia na avaliação de dispneia como sintoma de insuficiência cardíaca, seja ela por disfunção ventricular sistólica ou diastólica. O principal sinal para a liberação do ANP é a distensão das paredes dos átrios cardíacos. A ativação do BNP é regulada em resposta a aumentos de pressão nos átrios e ventrículos cardíacos. A concentração do BNP na corrente sanguínea pode ser influênciada por diversos fatores, como doenças cardíacas, idade insuficiência renal e sepse. Estudos iniciais com BNP na avaliação de dispneia demonstraram que sua dosagem consistia em importante preditor de insuficiência cardíaca quando comparado à dispneia de outras causas, com ponto de corte de 100 pg/ml; valores acima de 400 pg/ml têm alto valor predictivo positivo...

Natriuretic peptides are biomarkers released by the heart and vascular endothelium, with an important role in homeostasis regulation. They participate in the physiology of the kidneys and the heart and play a pathophysiological role in heart failure, hypertension and kidney disease. Among the natriuretic peptides, the most important are the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP). Currently, several studies have shown its importance in assessing dyspnea as a symptom of heart failure, due to systolic or diastolic ventricular dysfunction. The main sign for ANP release is the distension of atrial walls. BNP activation is regulated in response to pressure increases in the atria and ventricles. BNP blood concentration may be influenced by different factors, such as heart diseases, age, renal failure and sepsis. Early studies with BNP in the assessment of dyspnea have shown that its dosage was an important heart failure predictor when compared to dyspnea due to other causes, with a cutoff of 100 pg/ml; values higher than 400 pg/ml have a high positive predictive value for the diagnosis of dyspnea of cardiac origin. BNP may be used as a diagnostic and prognostic tool in heart failure. Its blood concentration is directly related to the New York Heart Association functional class and higher values are associated with poor survival, independent of the severity of left ventricular ejection fraction. The treatment of heart failure guided by BNP levels may improve the morbidity and mortality of chronic heart failure.

The broad homeostatic role of natriuretic peptides / O amplo papel homeostático dos peptídeos natriuréticos

A brief non-inclusive review on natriuretic peptides (NP), their receptors, and their main functional properties is presented. The three main NP, atrial (ANP), brain (BNP) and C-type (CNP) are considered. Guanylyl cyclase receptors modulate all the known systemic effects of NP. Clearance receptors determine the metabolic disposal of NP and in this manner regulate their plasma levels and/or local tissue concentrations. Structure-function properties, and homeostatic properties of NP receptors are presented. ANP, which plays a major role in pressure-volume homeostasis, is discussed in relationship to its effects on renal hemodynamic and excretory functions, inhibition of the renin-angiotensin-aldosterone system, vasorelaxant, and third-spacing action. For BNP special attention is directed to its role as a negative modulator of ventricular remodeling, in view of its anti-hypertrophic, anti-fibrotic and anti-inflammatory effects in the heart. The major effect of CNP in promoting vertebral and longitudinal bone growth is briefly addressed. Finally, emphasis is placed on the recent discovery that ANP affects fat metabolism in humans due to its powerful lipolytic action.

Este trabalho apresenta uma breve revisão parcial sobre os peptídeos natriuréticos (NP), seus receptores e suas principais propriedades funcionais. Serão discutidos os três principais NP: atrial (ANP), cerebral (BNP) e tipo-C (CNP). Os receptores guanilil-ciclase modulam todos os efeitos sistêmicos conhecidos dos NP. Receptores de clareamento determinam o catabolismo dos NP e, desta maneira, regulam seus níveis plasmáticos e/ou sua concentração tecidual. As propriedades do tipo estrutura-função e homeostáticas dos receptores de NP são apresentadas. O ANP, que tem um importante papel na homeostase pressão-volume, é discutido em relação aos seus efeitos sobre a hemodinâmica renal e funções de excreção, inibição do sistema renina-angiotensina-aldosterona, vaso-relaxamento e ação no terceiro espaço. Quanto ao BNP, especial atenção é focada no seu papel como um modulador negativo da remodelação ventricular, em vista de seus efeitos anti-hipertróficos, anti-fibróticos e anti-inflamatórios no coração. O principal efeito do CNP em promover crescimento ósseo vertebral e longitudinal é discutido brevemente. Finalmente, enfatiza-se a recente descoberta de que o ANP afeta o metabolismo de gorduras em humanos, devido à sua poderosa ação lipolítica.

Relação das pressões atriais com o peptídio natriurético atrial e seus efeitos na diurese e natriurese durante operação cardíaca com circulação extracorpórea / Variations of the atrial natriuretic peptide (ANP) introduced by estracorporeal circulation (ECC) during cardiac surgery

OBJETIVO: Estudar as variações do peptídio natriurético atrial (PNA) introduzidas pela circulação extracorpórea (CEC) durante operação cardíaca e testar a hipótese de que existe correlação entre os níveis plasmáticos de PNA, pressão atrial direita (PAD) pressão atrial esquerda (PAE), diurese e natriurese. MÉTODO: Estudo de coorte de 15 pacientes submetidos a revascularização do miocárdio com CEC. Os intervalos de tempo de observação foram: t0 = 10 minutos antes da CEC (valor controle); t1 = 10 minutos depois de fluxo total em CEC; t2 30 minutos em fluxo total em CEC; t3 = fase final da CEC em temperatura nasofaringeana de 36º C; e t4 = 30 minutos após o término da CEC. RESULTADOS: Os valores do PNA, PAE e PAD variaram significativamente (p<0,001). O PNA diminuiu de t0 para t1 (NS) e após elevou-se progressivamente até t4 (p<0,001). A PAE e a PAD reduziram (p<0,001) entre t0 e t1, elevando-se progressivamente até t4 (p<0,001). O Na+ urinário aumentou entre t0 e t3 (p<0,001), com queda em t4. A diurese aumentou progressivamente em todos os tempos considerados (p<0,001). Foi encontrada correlação significativa entre PNA e o volume de diurese no t0, coeficiente de correlação de 0,535 (p=0,040), e no tempo igual a t2 entre PNA e PAD, coeficiente de correlação de 0,590 (p=0,021). CONCLUSÃO: As concentrações do PNA apresentam variações durante a operação de revascularização com CEC, o que favorece o conceito de estar relacionadas com as pressões atriais, e ao término da CEC, têm uma importante função na excreção de sódio e no volume da diurese

Péptidos natriuréticos atriales / Atraial natriuretic peptides

Se realiza una revisión bibliográfica sobre los péptidos natriuréticos atriales. Se revisa su fisiología, se destaca su importancia en la regulación hídrica del organismo, así como sus alteraciones y su papel terapeútico en diversas condiciones.

Neurohypophyseal hormones and atrial natriuretic peptide in the control of body fluid homeostasis

Mammals control the volume and osmolality of their body fluids by stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+-receptors (plasma osmolality or sodium concentration) and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrative response, which depends on the integrity of the anteroventral region of the third ventricle, e.g. organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. In addition, the paraventricular, supraoptic and suprachiasmatic nuclei are also important structures involved in hydromineral balance. The hypothalamo-neurohypophyseal system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and non-osmotic stimuli. The natriuretic factor in the heart, which is released by the distension of the atria, leading to natriuresis and a myorelaxing action on vascular smooth muscle, also contributes to the hydromineral balance. In addition to the natriuretic factor in the heart, the identification of a natriuretic factor in the central nervous system mediating natriuresis was also demonstrated by purification of hypothalamic extracts. Therefore, the presence of the natriuretic factor in the heart and in the central nervous system allowed the characterization of a neuroendocrine system controlling body fluid homeostasis.

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

The release of adrenocorticotropin (ACTH) from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH). Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC) in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Stress and water balance: the roles of ANP, AVP and isatin.

Stress is often associated with water retention and its resolution with diuresis. The biological systems for the control of stress and water balance are very closely related. Corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) are co-localised in the hypothalamus and often act synergistically. Atrial natriuretic peptide (ANP) can exert a feedback control on the hypothalamic/pituitary/adrenal axis. ANP has been shown to be anxiolytic, whereas AVP may be anxiogenic. AVP and ANP levels have been found to be abnormal in a range of stress disorders and psychiatric illnesses. Isatin is an endogenous anxiogenic factor which is also a potent inhibitor of the ANP receptor. It may provide a link between the function of monoamines during stress, and the control of water balance by ANP.

La glucosa en conjunto con péptidos derivados de cininógenos podrían actuar desde el aparato digestivo como bloqueadores de la acción diurética-natriurética del péptido natriurético auricular / Glucose in conjunction with peptides derived from kininogens might act from digestive tract as blockers of ANP mediated diuresis-natriuresis

This paper describes long term research efforts wich have lead: 1) to the identification of peptides present in pepsanurin, a peptidic fraction obtained by pepsin hydrolisis of plasma globulins that inhibits the renal excretory action of atrial natriuretic peptide (ANP) and 2) to the discovery of an unexpected role of glucose, as a requisite, for these inhibitory effects. The active peptides identified in pepsanurin are derived from plasma kininogens, substrates of the kallikrein-kinin system. Pro-kinins of 15, 16 and 18 aminoacids, and bradykinin itself, block ANP-induced diuresis and natriuresis when injected iv, ip or into, the duodenal lumen of anesthetized rats in picomol doses. Furthermore, a novel 20 aminoacids fragment derived from kininogen dominium-1, named PU-D1, is the most potent and longer lasting blocker of ANP renal effects. The anti-ANP effects of those peptides are prevented by B2- kinin receptor antagonists. The inhibition of ANP by kinins and PU-D1 was evident only in rats infused with isotonic glucose; whereas the excretory effect of ANP was not affected in fasted rats not infused, or infused with saline. These findings provide evidence that glucose facilitates liquid retention through a kinin-mediated inhibition of ANP excretory action that may be related to the prandial cycle

Fator atrial natriurético: uma revisão direcionada / Factor atrial

Estudou-se o fator atrial natriurético (FAN), analisando-se a sua estrutura bioquímica, a fisiologia e a sua interação em situações de adaptação fisiológica, nas cardiopatias e em outras doenças. Foi feita uma revisão dos métodos de diagnóstico e o seu valor, como elemento preditivo de gravidade das doenças. Especulou-se sobre a sua potencial aplicabilidade na prática clínica e utilidade terapêutica

Aspectos reciente en la fisiopatología de la hipertensión arterial / New aspects in the physiopathology of arterial hypertension

En este trabajo analizamos los conocimientos recientes sobre los diversos mecanismos que se han relacionado con la fisiopatología de la hipertensión arterial esencial, su relación con el daño orgánico, principalmente aterosclerótico, las bases para tratamientos más específicos en el futuro, y la posibilidad de correcciones de tales alteraciones con los fármacos disponibles en la actualidad

Nuevas teorías fisiopatogénicas en la hipertensión arterial / New psysiopathogenic theories about high-blood pressure

Se hace una revisión de las más recientes teorías que tratan deexplicar la patogenia de la hipertensión arterial. Las acciones del péptido atrial natriurético a nivel glomerulotubular en relación con la excreción de sodio y agua y la inhibición de la liberación de sustancias vasoactivas, son abordadas al relacionar esta sustancia con las variaciones de la presión arterial, asimismo se hacen consideraciones sobre neuropéptido Y producido principalmente a nivel a sistema nervioso central y admitido un potencializador de las acciones vasoconstrictoras de la noradrenalina. También se exponen los criterios más actuales sobre el papel de las prostaglandinas vasodilatadoras en el desencadednamiento de las cifras altas de presión arterial en aquellos sujetos que al parecer presentan un hipoprostaglandinismo renal; se esbozan las perspectivas terapéuticas en este sentido con sustancias capaces de incrementar la liberación de prostaglandinas. Finalmente se hace resaltar el importante papel del endotelio vascular como verdadero órgano productor de sustancias biológicamente activas, principalmente el factor relajante derivado del endotelio identificado como óxido nítrico y en especial el factor contráctil conocido como endotelina, su relación con estímulos diversos, sus interacciones biológicas y su posible participación en la génesis y consecuencias hemodinámicas de la hipertensión arterial

Does plasma ANP participate in natriuresis induced by alpha-MSH?

Alpha-Melanocyte-stimulating hormone (alpha-MSH;0.6 and 3 nmol) microinjected into the anteroventral region of the third ventricle (AV3V) induced a significant increase in diuresis without modifying natriuresis or kaliuresis. Intraperitoneal (ip) injection of alpha-MSH (3 and 9.6 nmol) induced a significant increase urinary sodium, potassium and water excretion. Intraperitoneal (3 and 4.8 nmol) or iv (3 and 9.6 nmol) administration of alpha-MSH did not induce any significant changes in plasma atrial natriuretic peptide (ANP), suggesting that the natriuresis, kaliuresis and diuresis induced by the systemic action of alpha-MSH can be dissociated from the increase in plasma ANP. These preliminary results suggest that alpha-MSH may be involved in a gamma-MSH-independent mechanism of regulation of hydromineral metabolism.

Interactions of ANP and ANG II in tubular nephron acidification

In order to examine the effects and the interaction of angiotensin II (ANG II, 1 pM) and atrial natriuretic peptide (ANP, 1 muM) on the kinetics of bicarbonate reabsorption in the rat middle proximal tubule, we performed in vivo experiments using a stopped-flow microperfusion technique with the determination of lumen pH by Sb microelectrodes. These studies confirmed that ANG II added to the luminal or peritubular capillary perfusion fluid stimulates proximal bicarbonate reabsorption and showed that ANP alone does not affect this process, but impairs the stimulation caused by ANG II. We also studied the effects and the interation of these hormones in cortical distal nephron acidification. Bicarbonate reabsorption was evaluated by the acidification kinetic technique in early (ED) and late (LD) distal tubules in rats during in vivo stopped-flow microperfusion experiments. the intratubular pH was measured with a double-barreled microelectrode with H+ -sensitive resin. The results indicate that ANG II acted by stimulating Na+/H+ exchange in ED (81 per cent) and LD (54 per cent)segments via activation of AT1 receptors, as well as vacuolar H+ -ATPase in LD segments (33 per cent). ANP did not affect bicarbonate reabsorption in either segment and, as opposed to what was seen in the proximal tubule, did not impair the stimulation caused by ANG II. To investigate the mechanism of faction of these hormones in more detail, we studied cell pH dependence on ANG II and ANP in MDCK cells using the fluroescent probe BCECF. We showed that the velocity of cell pH recovery was almost abolished in the absence of Na+, indicating that it is dependent on Na+/H+ exchange. ANP (1 muM) alone had no effect on this recovery but reversed both the acceleration of H+ extrusion at low ANG II levels (1 pM and 1 nM), and inhibition of H+ extrusion at higher ANG II levels (100 nM). To obtain more information on the mechanism of interation of these hormones, we also studied their effects on the regulation of intracellular free calcium concentration, [Ca2+]i, monitored with the fluorescent probe Fura-2 in MDCK cells in suspension. The data indicate that the addition of increasing concentrations of ANG II (1 pM to 1 muM) to the cell suspension led to a progressive increase in [Ca2+]i to 2-3 times the basal level.In contrast, the addition of ANP (1 muM) to the cell suspension led to a very rapid 60 per cent decrease in [Ca2+]i and reduced the increase elicited by ANG II, thus modulating the effect of ANG II on [Ca2+]i. These results may indicate a role of [Ca2+)i in the regulation of the H+ extrusion process mediated by Na+/H+ exchange and stimulated/impaired by ANG II. The data are compatible with stimulation of Na+/H+ exchange by increases of [Ca2+]i in the lower range, and inhibition at high [Ca2+]i levels.

ANP as a neuroendocrine modulator of body fluid homeostasis

The role played by the central nervous system (CNS) in the control of body fluid homeostasis has been demonstrated by several authors. The AV3V plays a key role in central control of sodium excretion since its cholinergic, adrenergic, angiotensinergic and osmotic stimulation enhances and its destruction blocks sodium excretion in rats and goats. Cholinergic stimulation of the AV3V induced an increase in plasma ANP as well as a marked elevation in content of the peptide in medial basal hypothalamus, neuro and adenohypophysis. On the other hand, a decline in plasma ANP after AV3V lesions was accompanied by dramatic declines in content of ANP in these same structures. Our previous work has also indicated the essential role of the AV3V region and its ANPergic neurons in the control of ANP release in response to volume expansion (BVE) and indicated that alpha-adrenergic and muscarinic receptors are critical in mediating these responses. Lesions of the AV3V region, or of the median eminence or posterior lobe of pituitary gland blocked the increase in plasma ANP concentration in response to BVE. That this effect is related to blockage of the activity of the brain ANPergic neurons is supported by fyndings in sheep and in rats that the injection of the antiserum directed against ANP into the AV3V region at least partially blocked the BVE-induced release of ANP. We and others have also previously shown that denervation of baroreceptors inhibits ANP release induced by BVE. Activation of the ANP neurons also cause release of ANP from the anterior and neural lobe of pituitary gland. ANP neurons may activate oxytocinergic neurons in the supraoptic and paraventricular, which projects to neural lobe. Oxytocin would circulate to the atria and may directly activate release of ANP from the atrial myocytes, since i.v. or i.p. injection of oxytocin increases sodium excretion as well as elevates plasma ANP. Oxytoxin is present in the neural lobe in large quantity, which could reach the atria myocytes in high concentration and release ANP that circulate to the kidneys and evokes natriuresis to return circulating blood volume to normal.

Natriuretic peptides in the rat ofactory system

The olfactory system plays an important role in the mobilization of animal behaviour, along with the sense of taste. These functions are mediated by a complex olfactory structure composed of peripheral (olfactory epithelium) and central (olfactory bulb) components. Several neuropeptides are synthesized in the olfactory system and are believed to be involved in olfactive processing. Recently, another bioactive substance, atrial natriuretic peptide (ANP), has been demonstrated in the olfactory system. ANP is a potent diuretic, natriuretic and vasorelaxant hormone which, originally, was isolated from mammalian atria, but its gene is expressed in many loci. ANP is only one member of the natriuretic peptide (NP) family, which includes two other peptides, BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide) derived from different genes. All three peptides show many common features. A high concentration of ANP-immunoreactive varicose fibers has been detected in the rat olfactory nerve layer and glomerular layer of the olfactory bulb (OB). An important group of perykarya and thin varicose fibers has been observed in the olfactory tubercle. We have demonstrated the presence of both ANP precursor and ANP gene transcript in the rat olfactory bulb. In addition to synthesizing ANP, the OB contains ANP transducing receptors coupled to guanylyl-cyclase system. The immunoreactive ANP has also been detected in the rat olfactory mucosa (OM), where ANP has been localized in secretory cells of Bowman's gland and in the cells of the epithelial layer. The relatively low concentration of ANP in OM (2.5 ng/mg protein) suggests a local role for ANP, a hypothesis which is strengthened by the presence of ANP high affinity receptors in this tissue. Although the role of ANP in the olfactory system is not yet clear, ANP has been shown to modulate olfactory bulb mitochondrial membrane activity and to be involved in the olfactive function.