Atrial natriuretic peptide (ANP): response to NaCl is attenuated in rat atria in vitro after hypophysectomy

The present study documents the effects of hypophysectomy on the NaCl-stimulated release and on the basal secretion rates of ANP from rat atria in vitro. Three weeks before the experiments rats were subjected to hypophysectomy or to a corresponding sham operation. Atria were excised and superfused in an organ bath with a physiological buffer solution (PBS, 294 mosmol kg-1). After a control period of 5 min, superfusion was made with hyperosmotic NaCl (330 mosmol kg-1) for 10 min, and then again with PBS, but now for 15 min. Atria were paced with field stimulation (4 Hz, 20 V, 1 ms) and the resting tension was kept at 5 mN. The sham-operated animals responded with a significant increase (P less than 0.05) in the secretion rate of ANP (from 137 +/- 13 pg ml-1 [n = 35] to 235 +/- 24 [n = 34], means +/- SE) to the NaCl stimulus. The hypophysectomy blunted the ANP response to hyperosmotic NaCl. In addition, basal secretion rate was significantly (P less than 0.001) lower in the hypophysectomized than in the sham-operated animals during the whole experiment. Gel filtrations revealed that, during the hyperosmotic NaCl, both groups secreted exclusively ANP 1-28. We conclude that hypophysectomy blunts the basal as well as stimulus-induced in-vitro release of ANP from rat atria.     

Atrial natriuretic peptide involvement in human platelet aggregability in vitro

Summary Atrial natriuretic peptide (ANP) counteracts the destabilization and aggregation of platelets which is induced by vasopressin, angiotensin, and adrenaline.Abbreviations ADP Adenosinediphosphate - ANP Atrial natriuretic peptide     

Atrial natriuretic peptide response to endurance physical training in the rat

Summary The effect of an endurance physical training programme on the plasma and atrial natriuretic peptides (ANP) and on renal glomerular ANP receptors was evaluated in male normotensive Wistar rats. Maximal O₂ uptake was significantly greater in the endurance trained (117.1 Ml O₂ · kg^–1 · min^–1, SEM 6.18 versus the control rats 84.2 ml O₂ · kg^–1 · min^–1, SEM 4.88, P<0.01. In addition, various muscle oxidative enzymes were also significantly higher in endurance trained animals. An increase in resting plasma [ANP] was observed after 11 weeks of physical training (40.02 pg · ml^–1, SEM 7.07 vs 22.8 pg.ml^–1, SEM 3.83, P<0.05). Glomerular ANP receptor density was lower in trained rats (272 fmol · mg^–1 protein, SEM 3.1 vs 380 fmol · mg^–1 protein, SEM 6.1, P < 0.05), whereas atrial tissue [ANP] was not significantly different between controls and trained animals. However, in trained rats, circulating [ANP] was closely correlated with left atrial [ANP] (r = –0.92, P<0.05). Resting systolic blood pressure had not changed at the end of this physical training programme. It is considered that under physiological conditions ANP may be involved in long-term extracellular fluid volume homeostasis through the regulation of renal glomerular ANP receptors, and that the left atrium might play a significant role in this long term fluid volume control.     

Atrial natriuretic peptide in peripheral organs other than the heart

Summary The heart atria represent the major site of synthesis of atrial natriuretic peptide (ANP) in mammals including man, and its function as a regulator of water and salt homeostasis has been repeatedly suggested. However, more recently ANP has been located in organs not intimately related to cardiovascular physiology, e.g. the adrenals, lungs, and gut, as well as tissues belonging to the lymphatic, reproductive or endocrine systems. Thus, ANP might serve many more physiological roles than originally thought, but the functional significance of ANP in these non-cardiac tissues is presently poorly understood.Abbreviations ANP atrial natriuretic peptide - IR-ANP immunoreactive atrial natriuretic peptide - LH luteinizing hormone - ACTH adrenocorticotrophic hormone - RP-HPLC reverse phase high pressure liquid chromatography - mRNA messenger ribonucleic acid - RIA radioimmunoassay - CNS central nervous system     

Atrial natriuretic peptide and its mRNA in heart and brain of vasopressin-deficient Brattleboro rats

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Long-Evans rats (LE) served as controls. DI + DDAVP rats were given for 3 days sc. injections of 0.5/g l-desamino-8-D-arginine vasopressin in 1 ml. saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI + DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 + 4.4 vs. 3.4 + 0.6 ng mg“¹ tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 ± 0.2 vs. 1.3 + 0.2 and 0.5 + 0.1 vs. 1.3 + 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI + DDAVP rats than in LE rats (9.3 ±1.3 vs. 14.5 ±±1.6 and 6.1+0.6 vs. 14.5 ± 1.6 pg mg^-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change. Desmopressin increased the ANP concentration in the right ventricle of DI rats. Thus the correction of the complete vasopressin deficiency-does not appear to associate with synthesis or release of atrial natriuretic peptide in heart or hypothalamus.     

Origin and characterization of atrial natriuretic peptide in the rat parotid gland

Summary The heart atria represent the major site of synthesis for atrial natriuretic peptide (ANP) which exerts potent natriuretic, diuretic and vasoactive functions. Recently, ANP-immunoreactivity has been detected in extracardial organs involved in water and electrolyte homeostasis, such as the intestine and certain exocrine glands. The present study investigates ANP in the parotid gland. It was found by immunohistochemical techniques that the peptide is localized in ductal cells of the gland. An analysis of the immunoreactive material by high-pressure liquid chromatography and radioimmunoassay revealed the prohormone of ANP (ANP 1-126) and the biologically active fragment (ANP 99-126). Furthermore, Northern blot hybridization disclosed the presence of mRNA coding for ANP. It is suggested that ANP is synthesized and released from the parotid gland and functions in the control of saliva production.     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (P_sf) was increased from 18.5 to 25.7 nl min^-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.     

慢性心房颤动患者血清ANP和BNP水平的变化

目的:研究慢性心房颤动(CAF)患者血清心房利钠肽(ANP)、脑利钠肽(BNP)水平的变化及其临床意义。方法:放射免疫分析测定102例CAF患者、40例无CAF患者和30例对照组的血清ANP、BNP水平,并进行统计分析。结果:CAF组血清ANP和BNP水平均显著高于无CAF组和对照组(P均<0.01);无CAF组血清BNP显著高于对照组(P<0.01),但ANP与对照组无显著差异(P>0.05),CAF组中ANP与BNP成显著正相关(P<0.01)。CAF患者中Ⅰ、Ⅱ、Ⅲ、Ⅳ级心功能组间平均血清ANP、BNP水平依次显著性递增(P<0.01)。住院期间死亡组血清ANP和BNP水平也显著高于好转出院组(P<0.05,P<0.01)。结论:CAF患者血清ANP和BNP水平显著增高,并随心功能分级依次递增,死亡组更高。     

Plasma atrial natriuretic peptide (ANP) concentration and fluid balance during rapid intravenous saline infusions in camels

Human muscle samples were obtained with the percutaneous biopsy technique. The samples were membrane-hyperpermeabilized (skinned) using a chemical or freeze-drying technique. Short single fibre segments were dissected from the sample, transferred to an experimental chamber, connected to a force transducer and manipulator, and exposed to temperature-controlled solutions. The force generating-capacity, the sensitivity of the contractile apparatus to calcium and the caffeine threshold for calcium release from the sarcoplasmic reticulum could be studied in the short muscle fibre segments obtained from man with the percutaneous muscle biopsy technique. The average length of the fibre segments between the connectors was 0.44±0.21 mm. Thus, detailed studies of the contractile machinery can be made on human skinned muscle fibres with only minimal discomfort to the patient or subject during biopsy, which should be useful in studies of neuromuscular disease, muscle plasticity or in applied physiology.     

妊高征患者母血脐血中内皮素及心钠素的变化

应用放射免疫法测定１５例妊高征患者，１５例正常妊娠妇女母血和脐血中心钠素与内皮素含量。结果：妊高征组母血和脐血中心钠素均明显高于正常妊娠组（Ｐ＜０．０１），妊高征组母血中内皮素明显高于正常妊娠组（Ｐ＜０．０１），而两组脐血内皮素无明显差别（Ｐ＞０．０５），各组心钠素与内皮素之间均有明显正相关（Ｐ＜０．０１）。说明内皮素在妊高征发病中起重要作用。而心钠素在抑制妊高征发生中应起一定作用；心钠素与内皮素之间相互影响。     

Increased duodenal HCO3 output after blood volume expansion in the rat: an effect mediated by atrial natriuretic peptide (ANP)?

Duodenal HCO3^- secretion was measured by in-situ titration in chloralose-anaesthetized rats. The effects of hypervolaemia, induced by i.v. injections of an albumin infusion, on duodenal HCO₃^- secretion were investigated. A 10% increase in blood volume increased duodenal HCO₃^- secretion by about 50%, and this effect was unaffected by splanchnicotomy. If the splanchnicotomy was combined with cervical vagotomy, the basal HCO₃^- secretion was lower but the increase in secretion after 10% blood volume expansion with albumin was still 50%. If the same increase in blood volume was produced in splanchnicotomized and vagotomized rats in which the right atrial appendix had been removed, a procedure that markedly reduces the ANP (atrial natriuretic peptide)-producing cells, no increase in secretion could be observed. Intravenous injections of α-r-ANP (10 μg kg^-1 and 30 μg kg^-1) increased duodenal HCO₃^- secretion in a dose-dependent fashion. Based on the present findings, we suggest that hypervolaemia increases duodenal HCO₃^- secretion via release of ANP from the heart.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

COPD患者血清ANP、BNP和CNP测定及其临床意义

目的：探讨慢性阻塞性肺疾病（COPD）患者血清心钠素（ANP）、脑钠肽（BNP）、C型钠尿肽（CNP）水平的变化及其临床意义。方法：采用放射免疫分析79例COPD患者和36例健康对照组血清ANP、BNP和CNP水平,并进行统计分析。结果：COPD组血清ANP、BNP和CNP水平显著地高于健康对照组（t=3.6841,P〈0.01;t=11.70,P〈0.01;t=2.177,P〈0.05）,但Ⅰ、Ⅱ、Ⅲ和Ⅳ级组间血清ANP、BNP和CNP水平方差检验无显著性意义（F=2.123、F=1.515、F=0.165,P均〉0.05）。相互间相关性分析揭示：ANP、BNP和CNP三者间均呈显著正相关（r=0.369,P〈0.01;r=0.354,P〈0.01;r=0.426,P〈0.01）。住院期间死亡的患者血清ANP、BNP和CNP水平显著地高于好转出院的患者（t=5.149,P〈0.01;t=4.875,P〈0.01;t=2.830,P〈0.01）。结论：COPD患者血清ANP、BNP和CNP显著升高,且与病人的稳定情况、肺动脉压力及预后相关。     

Localization of 125I-atrial natriuretic peptide (ANP) in the rat fetus.

Summary In this in vitro autoradiographic study of ANP-binding sites in fetal rats, ¹²⁵I-ANP bound to receptors in certain developing neural crest derivatives, including the boundary caps, dorsal root ganglia, and Schwann cells of peripheral nerves. Within the spinal cord, ANP receptors were localized in the roof plate and floor plate. The developing meningeal layer of the CNS, blood vessels, lung, liver, and wall of the herniated gut were also labeled. The topographical and temporal correlation of the appearance of ANP receptors with the developmental processes of the targets suggests that ANP in the fetus is multifunctional, and may be involved in diverse events such as gliogenesis, formation of axonal pathways or surfactant production.     

Localization of 125I-labelled α-r-atrial natriuretic peptide in rat tissues by whole-body and microautoradiography

¹²⁵I-labelled α rat atrial natriuretic peptide (28 amino acids: Ser 99–Tyr 126) ([¹²⁵I]α-rANP) was given i.v. to Sprague—Dawley rats and the distribution of radioactivity in the tissues was examined by whole-body and microautoradiography at intervals from 2 min to 4 h after the administration. Inhibition of uptake of the [¹²⁵I]α-rANP by simultaneous injection of an excess of non-labelled α-rANP was taken as an indication that highly labelled structures in rats injected with [¹²⁵I]α-rANP alone are due to an abundance of specific receptors for the peptide. In the rats given only the [¹²⁵I]α-rANP a rapid and high radioactivity occurred in the renal glomeruli, the endocardium of the heart ventricles, the endothelium of the processus ciliares of the eyes, the portal vessels and a few larger vessels of the liver, the subcapsular vessels of the adrenal glands and the parenchyma of the lungs. Other tissues showing a distinct, but less prominent, radioactivity were the endocardium of the heart atria, the walls of the great afferent and efferent vessels in the thoracic cavity, the choroid plexuses of the brain ventricles, the pia mater, brown fat, the muscularis layer of the stomach and the intestines, the lamina propria of the villi in the small intestine and the walls of a few small blood vessels in the kidney medulla. The specific labelling was highest at 2 min after injection and then diminished at later intervals. Several of the labelled structures are localized in tissues involved in the regulation of blood pressure, and fluid and electrolyte homeostasis, processes in which the atrial peptides are considered to play a role. It is suggested that high concentrations of receptors are present at the sites at which the [¹²⁵I]α-rANP was strongly localized and that biological effects of the atrial peptides are exerted via these structures.     

Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome

Elevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non-rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end-apnoeic oxygen saturation and end-apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end-apnoeic systolic transmural pulmonary artery pressure (P(PATM)) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235+/-0.088 vs. 0.207+/-0.057 nmol/L). However, the highest levels were found during exercise (0.334+/-0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable.     

Increase in atrial natriuretic peptide in response to physical exercise

Summary Circulating atrial natriuretic peptide (ANP) level was determined during physical exercise to investigate the correlation between changes in ANP level and heart rate increases.Six subjects exercised at a work level of 75% for 30 min, two also performed two successive exercises at 75% while two more exercised for longer at 55% · Plasma ANP levels and heart rate increased in all the exercising subjects. At the end of the exercise, the ANP level fell immediately, suggesting an immediate reduction in ANP secretion by the heart. Pre-exercise values were reached after 30 min. Successive exercises gave the same heart rate related ANP patterns without previous secretory episodes having any effect. These results lead to the conclusion that ANP intervenes in the cardiovascular adjustments to exercise.     

Expression and glucocorticoid regulation of natriuretic peptide clearance receptor (NPR-C) mRNA in rat brain and choroid plexus

The natriuretic peptide clearance receptor (NPR-C) binds atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide with high affinity. This receptor lacks an intracellular guanylate cyclase domain, and is believed to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylate cyclase. The present report summarizes the first detailed mapping of NPR-C mRNA in rat brain. In situ hybridization analysis revealed high levels of NPR-C mRNA expression in frontal and retrosplenial granular cortices, medial preoptic nucleus, ventral cochlear nucleus and choroid plexus. NPR-C mRNA expression was also observed in deep layers of neocortex and limbic cortex, posterior cortical amygdala, ventral subiculum, amygdalohippocampal area, and dentate gyrus. Positive hybridization signal was observed in both anterior and intermediate lobes of the pituitary gland. Regulatory studies indicated that expression of NPR-C mRNA was increased in the medial preoptic nucleus of adrenalectomized rats, suggesting negative glucocorticoid regulation. No changes in NPR-C mRNA expression were observed in frontal cortex or choroid plexus. These results suggest a role for the NPR-C in modulation of natriuretic peptide availability and/or adenylate cyclase activity in a subset of central natriuretic peptide circuits concerned with cortical, olfactory and neuroendocrine functions. Response of the NPR-C gene to changes in circulating hormones suggests the capacity for glucocorticoid modulation of natriuretic peptide action at the receptor level.     

心钠素免疫反应在豚鼠耳蜗中的整体分布

目的 :研究豚鼠耳蜗中心钠素 (ANP)免疫反应的分布状态 ,为探讨ANP在耳蜗中的作用提供形态学基础。方法 :采用免疫组织化学ABC法检测ANP在正常豚鼠耳蜗各组织中的分布特征。结果 :在耳蜗 1～ 4回的血管纹、螺旋缘、Corti’s器、螺旋神经节和中间阶外壁的螺旋韧带均发现有ANP反应 (ANP IR)阳性产物 ;而耳蜗骨壁、前庭膜、鼓阶外壁的螺旋韧带和鼓阶的下壁ANP IR为阴性。结论 :耳蜗中的ANP在内耳淋巴液的生成和声信号的传导以及耳蜗血流量的调节等方面可能担负着重要的作用     

Atrial natriuretic factor (ANF) does not affect ion transport in human intestine but does in porcine intestine

The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (I_sc) was measured subsequent to serosal application of ANF (10^--⁶ m), 8–Br-cyclic guanosine monophosphate (8–Br-cGMP) (10^--⁴ m), and theophylline (10^--² m). ANF did not affect I_sc whereas 8–Br-cGMP increased I_sc by 28 (8–53), 16 (3–36), and 16 (5–41) μA cm^-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6–8.9), 2.5 (0.4–4.0) and 0.9 (0.3–2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8–Br-cGMP. I_sc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10^--⁶ m) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in I_sc which was comparable to the 8–Br-cGMP response in humans. The porcine I_sc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10^--⁴ m) and BaCl₂ (10^--³ m), and mucosal application of the chloride-channel blocker diphenylamine-2–carboxylate (DPC) (10^--³ m). Mucosal amiloride (10^--⁵ m) pre-treatment reduced baseline I_sc but did not affect the porcine intestinal I_sc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the I_S0 response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.