Atrial natriuretic peptide (ANP) and N-terminal peptide of proANP (NT-proANP) in maternal and umbilical cord plasma in spontaneous labor and at elective cesarean section.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Leppäluoto.
Explore the source record for details and available documents.
OBJECTIVE: To investigate the relation between concentrations of endothelin and atrial natriuretic peptide (ANP) in maternal plasma and vasospasm in the uterine and umbilical arteries as detected by duplex pulsed colour Doppler ultrasonography in hypertensive pregnancies. DESIGN: An observational study. SUBJECTS: 32 women admitted consecutively to hospital with pregnancy induced hypertension (seven without proteinuria and 25 with proteinuria) and 78 healthy pregnant women examined at 28-40 weeks gestation. MAIN OUTCOME MEASURES: Systolic/diastolic (S/D) ratio in flow velocity waveforms (FVWs) and plasma concentrations of endothelin and ANP in the 32 women with pregnancy induced hypertension; plasma concentrations of endothelin and ANP in 78 healthy pregnant women (controls). RESULTS: Pathological FVWs suggesting vasospasm in the uterine or umbilical artery, or both arteries, were found in 12 women with hypertension. Plasma ANP was significantly higher (P = 0.03) in the women with hypertension and pathological FVWs (median 23.0, range 10.1-52.8 pmol/l) than in those with hypertension and normal FVWs, (median 13.8, range 5.3-42.3 pmol/l) but corresponding plasma endothelin levels did not show any significant difference (median 1.63, range 0.51-3.33 pmol/l and median 1.38, range 0.51-3.51 pmol/l, respectively). CONCLUSION: Local release of endothelin from the vascular endothelium is thought to cause vasospasm in pregnancy induced hypertension but this does not seem to increase the concentration of endothelin in the maternal peripheral plasma, probably because of its rapid disappearance from the blood circulation. As ANP dilates the blood vessels, the increase of its release in hypertensive pregnancies may be a compensatory mechanism against vasospasm.
Adrenergic regulatory mechanisms of melatonin synthesis and secretion were studied in the pigeon in vivo. Late-afternoon intraperitoneal injection of noradrenaline (NA; 1 mg/kg) resulted in a significant decrease in plasma melatonin levels in 3 h. The same effect was seen after phenylephrine treatment (1 mg/kg i.p.), indicating that an alpha 1-adrenergic mechanism may mediate the inhibition. Propranolol treatment had no effect on plasma melatonin levels, supporting this concept. Detomidine (1 mg/kg i.p.), an alpha 2-adrenergic agonist, increased melatonin levels. This stimulatory effect was blocked by yohimbine, an alpha 2-adrenergic antagonist. However, yohimbine alone had no effect on the plasma melatonin levels, suggesting that alpha 2-adrenergic transmission is not primarily responsible for the nocturnal stimulation of melatonin synthesis and secretion in the pigeon.
To determine the relationship between hyperosmolality and immunoreactive atrial natriuretic peptide of heart atrial plasma six healthy men were given 0.06 ml kg-1 min-1 855 mmol l-1 NaCl, i.v., for 2 h. The right atrial pressure and atrial plasma atrial natriuretic peptide were measured. During the infusion, right atrial pressure was kept constant by lowering the legs of the subject in a supine position downwards if any increase in the pressure was seen. There was a significant and linear increase in atrial serum osmolality, from 288 +/- 3.3 to 307 +/- 3.2 mOsm kg-1 (P less than 0.001). No statistically significant changes in right atrial pressure were seen. Regression analysis revealed that there was a statistically significant correlation between serum osmolality and plasma ANP in three subjects (responders) (r2: 0.5241, 0.8965, 0.6695). In three other subjects (nonresponders), there was no correlation between osmolality and ANP. The mean basal osmolality of responders was 280 mOsm kg-1 and the mean basal osmolality of nonresponders was 295 mOsm kg-1. In contrast, all subjects responded with an increase in plasma ANP (P less than 0.05) after RAP had been increased by tilting the legs of the subject upwards for 30 min. We conclude that the right atrial pressure regulates the release of atrial natriuretic peptide. Serum hyperosmolality may also contribute to the regulation of atrial natriuretic peptide independently of the right atrial pressure in man.
To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg-1 in 6 h). Serum ethanol levels increased to 27 +/- 4 mmol l-1 (mean +/- SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280 +/- 10 to 340 +/- 4 mosm kg-1 in 2 hours (P less than 0.01) and was 300 +/- 4 at 14 h (P less than 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 +/- 0.1 kg water in 2 h. Free water clearance increased from -3.4 +/- 1.4 to 2.8 +/- 1.5 ml min-1 in 2 h (P less than 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 +/- 2.1 to 3.3 +/- 1.3 ng l-1 (P = 0.05) in 30 min and increased to 17 +/- 25 and 12 +/- 10 ng l-1 at 6 and 12 h, respectively (P less than 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 +/- 9 to the minimum of 11 +/- 3 ng l-1 in 2 h (P less than 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 +/- 2, 165 +/- 153 and 143 +/- 101% (P less than 0.01 each) during 1-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the role of atrial natriuretic peptide (ANP) in exercise-related cardiovascular and hormonal adjustments in hypobaric conditions, 14 young athletes performed a maximal ergometer test in a hypobaric chamber adjusted to simulate the altitudes of sea level and 3,000 m. Plasma immunoreactive ANP levels rose from 5.89 to 35.1 pmol/l at sea level and rose significantly less (P less than 0.05), from 5.36 to 22.3 pmol/l, at simulated 3,000 m. Plasma immunoreactive amino-terminal peptide of proANP (NT-proANP) levels increased to the same extent at sea level and at simulated 3,000 m (from 240 to 481 pmol/l and from 257 to 539 pmol/l, respectively). Plasma immunoreactive aldosterone increased significantly less at simulated 3,000 m (P less than 0.05), but the changes in plasma renin were similar in both conditions. Plasma immunoreactive endothelin-1 and serum erythropoietin levels remained unchanged. In conclusion, we found a blunted ANP response to maximal exercise of ANP in acute hypobaric exposure compared with that in normobaric conditions, but no significant difference in the NT-proANP responses between the two conditions. The divergence may be due to stimulation of the elimination mechanism of ANP.
Daily patterns of pineal function were studied in different seasons in 10 adult semidomesticated female reindeer and 5 prepubertal calves living in a natural arctic environment at latitude 69 degrees 10'N. Serum samples for melatonin RIA were collected every 4 h for 24 h in October (10 h of light, 14 h of darkness and 8 h of light, 16 h of darkness), December (24 h of darkness), March (13 h of light, 11 h of darkness), and June (24 h of light). A significant daily variation in serum melatonin levels was observed in the adult reindeer, with peak values (20-50 ng/liter) occurring during the night in autumn, winter, and spring, but not summer. The daytime values at 13 h (5-10 ng/liter) were constant throughout the year. Total daily amounts of melatonin, the duration of peak levels, and maximal concentrations were significantly lower in spring and summer than before the rut in autumn. The exposure of adult animals to artificial darkness from bright sunlight on August 1 and September 21 resulted in an immediate increase in serum melatonin concentrations. The 2-week-old calves had detectable serum melatonin levels, but no daily rhythm in the spring, whereas a rhythm was detectable by the first autumn, only to disappear unexpectedly during the first winter and return in the spring. At the age of 16 months, the calves had serum melatonin concentrations similar to those in the adults. Our present results show that the continuous illumination experienced during the summer abolished the normal daily melatonin rhythm. This does not seem to be related to organic changes in the pineal gland, since exposure to darkness during the summer increased melatonin levels. The highest melatonin secretion occurred in the autumn and was evidently associated with the rut. Similarly, the daily melatonin rhythm of an adult type observed in the calves at the age of 16 months may be related to the observation that most calves were in rut. Thus, a high rhythmical melatonin secretion appears to relate to puberty and the initiation of heat in female reindeer.
Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced by endothelial cells. They are thought to regulate the local vasomotor tone with endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor substances yet identified and veins and renal vasculature are the most sensitive targets. They reduce cardiac output and have positive inotropic and chronotropic effects. ETs increase the secretion of atrial natriuretic peptide (ANP), aldosterone and catecholamines but reduce renal blood flow and glomerular filtration and they also have mitogenic properties. ETs bind to receptors (ETA and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin, thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene expression. Raised concentrations of plasma ET have been found to occur in several clinical conditions such as hypertension, myocardial infarction, cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease and surgical operations suggesting that ETs have a role in several patophysiological processes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The present study documents daily rhythms of plasma atrial natriuretic peptide, serum osmolality and haematocrit in the rat. One-hundred and twenty-five Sprague-Dawley rats were used. They were bred under a cycle of 12 h light/12 h dark starting at 07.00 h. Fifty-three rats were decapitated between 09.00 and 16.00 h (study I) and 72 rats in groups of six were decapitated at 2-h intervals for a period of 24 h (study II). In study I, plasma atrial natriuretic peptide was 156 +/- 11 pg mg-1 (mean +/- SEM). In study II, atrial natriuretic peptide was at a control level from 08.00 to 18.00 h and then began to increase. At 22.00 h, atrial natriuretic peptide was 420 +/- 105 pg ml-1, which was significantly higher than at 08.00 h (P less than 0.05). The serum osmolality was over 300 mosmol kg-1 during the day. The highest mean osmolalities (315, 317, 312 mosmol kg-1) were found from 18.00 to 22.00 h. These were significantly different (P less than 0.05) from other groups during the day. The haematocrit was highest at 14.00 h (49.5 +/- 0.7%) and lowest at 24.00 h (43.6 +/- 0.8%) (P less than 0.05). In conclusion, we have shown that there are significant daily rhythms of plasma atrial natriuretic peptide, serum osmolality and haematocrit during a 24-h period and 12 h light/12 h dark cycle in the rat.
Male volunteers were exposed to +10 degrees C ambient temperature for 2 hours while they were sitting undressed. The levels of endothelin-1 and atrial natriuretic peptide were determined by radioimmunoassays. Control samples were obtained at thermoneutrality. The cold exposure resulted in lowering of the mean skin temperature (from 31.2 +/- 0.3 degrees C-22.6 +/- 2.5 degrees C, mean +/- SEM), which indicates that a marked vasoconstriction took place, as well as a decrease of the body heat content (by 11.2 +/- 0.7 kJ kg-1). However, plasma endothelin-1 levels did not change significantly during the exposure. Thus circulating endothelin-1 does not seem to be responsible for the vasoconstriction associated with cold air exposure. The plasma atrial natriuretic peptide levels exhibited a slight increase towards the end of the cold exposure. This finding is in accord with the notion that atrial natriuretic peptide might contribute to the diuresis frequently observed in the cold.
Atrial natriuretic factor (ANF), a peptide hormone that regulates salt and water balance and blood pressure, is synthesized, stored, and secreted from mammalian myocytes. Stretching of atrial myocytes stimulates ANF secretion, but the cellular processes involved in linking mechanical distension to ANF release are unknown. We reported that phorbol esters, which mimic the action of diacylglycerol by acting directly on protein kinase C and the Ca2+ ionophore A23187, which introduces free Ca2+ into the cell, both increase basal ANF secretion in the isolated perfused rat heart. Phorbol ester also increased responsiveness to Ca2+ channel agonists, such as Bay k8644, and to agents that increase cAMP, such as forskolin and membrane-permeable cAMP analogs. In neonatal cultured rat atrial myocytes, protein kinase C activation by 12-O-tetradecanoylphorbol 13-acetate stimulated ANF secretion, whereas the release was unresponsive to changes in intracellular Ca2+. Endothelin, which stimulates phospholipase C mediated hydrolysis of phosphoinositides and activates protein kinase C, increased both basal and atrial stretch-induced ANF secretion from isolated perfused rat hearts. Similarly, phorbol ester enhanced atrial stretch-stimulated ANF secretion, while the increase in intracellular Ca2+ appeared to be negatively coupled to the stretch-induced ANF release. Finally, phorbol ester stimulated ANF release from the severely hypertrophied ventricles of hypertensive animals but not from normal rat myocardium. These results suggest that the protein kinase C activity may play an important role in the regulation of basal ANF secretion both from atria and ventricular cells, and that stretch of atrial myocytes appears to be positively modulated by phorbol esters.
The effects of passive heat exposure on atrial natriuretic peptide (ANP) were studied in six healthy men staying in a Finnish sauna at +92 degrees C for 20 min. Their rectal temperature increased by 0.4 degrees C, and evaporative water loss was 0.92 +/- 0.14 (SD) kg. Heart rate and systolic blood pressure increased significantly during the 20-min exposure. Serum osmolality and plasma arginine vasopressin levels increased during the exposure, then declined, and increased significantly again at 90-120 min. Plasma renin activity and aldosterone increased by two- to fourfold in 20 min. Plasma ANP levels rose from 13 +/- 7 to 39 +/- 15 ng/l at 60 min and to 41 +/- 13 ng/l at 120 min (P less than 0.01 for both). We conclude that transient increases in heart rate and systolic blood pressure or changes in blood volume as inferred from the weight loss do not contribute to the increased plasma ANP levels observed after the heat exposure. Instead, increased secretions of pressor hormones could explain the elevated plasma ANP levels observed after the thermal stress.
An extract of a pancreatic carcinoid tumor obtained at autopsy from a patient who had suffered from Cushing's syndrome was found to have the ability to release thyrotropin (but not any other pituitary hormones) from cultured rat anterior pituitary cells, and to bind to a specific thyrotropin-releasing hormone (TRH) antiserum. The tumor contained 2.2 and 3.9 nmol/g of TRH bio- and immunoreactivity, respectively. The active material was purified and its amino acid composition and chromatographic properties were found to be identical with those of synthetic ovine/porcine TRH. This represents the first isolation of human TRH and the first established case of a 'TRHoma', a TRH-producing tumor.
Mechanisms of atrial natriuretic peptide (ANP) release were studied in neonatal rat heart atrial and ventricular myocytes cultured on Cytodex 3 microcarriers. For simultaneous observations of cytosolic free calcium concentration ([Ca2+]f) and ANP secretion, the culture was packed in a chromatography column, inserted into the cell holder of a spectrofluorometer was perifused with a buffer solution. [Ca2+]f was measured by the fluorescent calcium indicator Fura-2 and ANP in the effluent perfusate by radioimmunoassay. No cell damage was observed and the basal ANP secretion rate and [Ca2+]f were comparable with values obtained by other methods. K(+)-induced depolarization raised [Ca2+]f by 50%, but it rapidly declined again to a steady level 10-20% above the baseline. The calcium channel agonist Bay k8644 elicited a similar temporal pattern of [Ca2+]f changes and 1 microM ionomycin induced a 100-fold increase in [Ca2+]f with a slow re-establishment of the original baseline. None of these stimuli increased the ANP secretion rate of the atrial or ventricular myocytes. Protein kinase C activation by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulated ANP secretion from the atrial myocytes, while the ventricular myocytes were unresponsive to TPA. It is concluded that Ca2+ is not the main mediator in the regulation of ANP release in cultured neonatal heart cells.
To evaluate the possible effect of the extreme and permanent changes in the hormonal milieu and in the lighting conditions at birth on the pineal hormone, melatonin (MT), we measured maternal vein and umbilical artery concentrations of MT in 19 parturients, post-partum urinary concentrations of MT in 14 mothers and their infants, and daytime (0800-2000 h) and night-time (2000-0800 h) urinary concentrations of MT and 6-sulphatoxymelatonin in 22 infants during the first 8 days of life. The mean MT concentrations in maternal venous blood and umbilical arterial blood did not differ significantly from each other and there was a positive correlation between them. The same was true for postpartum urinary MT of the mothers and their infants. There was no diurnal rhythm of MT during the first week of life. MT excretion in neonates was 2-5 pmol/12 h (only 1-5% in comparison with adults) and that of 6-sulphatoxymelatonin 150-300 pmol/12 h. In reverse phase high pressure liquid chromatography (HPLC) studies, 84-100% of total MT immunoreactivity was eluted at the same position as synthetic MT, and a small amount of hydrophobic MT-like immunoreactive material was also detected in five of the 10 urine extracts studied. This material (perhaps a novel neonatal metabolite of MT) may be indicative of immaturity of neonatal metabolism of MT although 6-hydroxylation is also functional in neonates. Although infant MT immediately after delivery at least partly reflects maternal MT secretion, our results show that the pineal gland is capable of producing MT at this time.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively. A significant correlation was found between the IR-ANP release from ventricles and ventricular weight to body weight ratio (r = 0.56, P < 0.01, n = 24). 4. These studies demonstrate that the ventricles contribute substantially to the circulating level of ANP, and that the amount released depends on the degree of ventricular hypertrophy.