Plasma atrial natriuretic factor concentrations and renal actions in the domestic fowl

Plasma atrial natriuretic factor concentrations in Rhode Island red hens averaged 72.1±6.9 pg·ml^-1, range 33.4–136.0 pg·ml^-1. The intravenous infusion of isotonic saline containing 3% dextran for 2 h produced no significant changes in plasma osmotic or electrolyte concentrations; however, haematocrit changes indicated vascular expansions of 14.4% after 1 h and 21.3% after 2 h and plasma atrial natriuretic factor concentrations were elevated by 190% and 257%, respectively. The intravenous infusion of chicken atrial natriuretic factor at rates of 10, 25, 50 and 100 ng·kg^-1·min^-1 for 20 min produced levels of plasma atrial natriuretic factor that were directly related to the infusion rate and which, in birds undergoing a steady-state diuresis/natriuresis driven by the intravenous infusion of isotonic saline at 1 ml·min^-1, produced dose-dependent increases of 19, 26, 38 and 55% in urine flow rate and of 8, 30, 49 and 77% in sodium excretion. Potassium excretion was significantly increased only at the two highest atrial natriuretic factor infusion rates. The observed correlation between plasma atrial natriuretic factor concentration and vascular volume together with the atrial natriuretic factor-induced modulation of renal salt and water elimination is consistent with the concept that in the chicken this peptide has a physiological role as a regulatory hormone in volume homeostasis.Abbreviations AII angiotensin II - ANF atrial natriuretic factor - AVT arginine vasotocin - BV blood volume - chANF chicken atrial natriuretic factor - CHE chicken heart extract - ECF extracellular fluid - EDTA ethylenediaminetetra-acetate - Hct haematocrit - i.v. intravenous - PCR plasma clearance rate - PRA plasma renin activity - RIA radioimmunoassay     

Atrial natriuretic factor in essential hypertension

We measured circulating levels of immunoreactive atrial natriuretic factor (ANF) in 10 patients with untreated, uncomplicated mild to moderate essential hypertension and in 15 normotensive controls. ANF concentrations were significantly higher in the hypertensive group than in the control group (38.4 +/- 6.9 pg/ml versus 18.3 +/- 1.8 pg/ml, p less than 0.02). A positive correlation between ANF levels and systolic, diastolic and mean blood pressure was noted in the total study population (p less than 0.008, r = 0.52; p less than 0.005, r = 0.55; p less than 0.02, r = 0.46, respectively). Thus, plasma ANF concentrations are elevated in essential hypertension and may result from increased intraarterial pressure.     

The ScaI gene polymorphism of the atrial natriuretic factor and essential arterial hypertension in childhood

In order to investigate the contribution of the atrial natriuretic factor (ANF) gene in pathogenesis of essential arterial hypertension (EAH), we analyzed the ScaI gene polymorphism of the ANF gene in a group of children with EAH. Fifty-eight children, aged 8-19 years, with the diagnosis of EAH were included in the association study and were compared to 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure higher than the 95th age-gender-height percentile of the adopted reference values. We failed to demonstrate an association between the ScaI ANF gene polymorphism and EAH in childhood (OR = 2; 95% CI 0.9-4.2; p = 0.07), however, we provided evidence of an interaction between the ScaI ANF gene polymorphism and obesity defined as BMI over the 85th percentile (OR = 13.1; 95% CI 1.6-106; p < 0.001).     

Plasma levels of atrial natriuretic factor in nonhibernating and hibernating marmots

Plasma atrial natriuretic factor (ANF) was measured in 16 marmots at various times of the year. Nonhibernating males (n = 6) had an average plasma concentration of 56 +/- 8 pg/ml; nonhibernating females (n = 6) had an average plasma concentration of 61 +/- 4 pg/ml. During hibernation an additional group of females (n = 4) showed an average of 25 +/- 5 pg/ml. Plasma ANF of both groups of nonhibernating marmots was significantly higher (P less than 0.01) than that the hibernating group, but there was no difference between nonhibernating males and females.     

Plasma atrial natriuretic factor and atrial wall stress in hypertensive and normotensive rabbits after pacing and volume expansion.

Atrial natriuretic factor (ANF) is present in high concentration in atria but in very low concentration in the ventricles. Under conditions of haemodynamic overload ventricular gene expression may become activated, but it is not clear if ventricular ANF can be released through a regulated or constitutive pathway. The purpose of this study was to determine whether basal and stimulated release of ANF are increased in perinephritic rabbits with mild hypertension. Six rabbits were rendered hypertensive by wrapping both kidneys in cellophane, and six sham-operated rabbits were used as controls. Eight weeks after renal wrapping, mean arterial pressure was approximately 20 mmHg higher in the experimental group. After anaesthesia, the renal-wrapped group had a higher vascular resistance. Right and left atrial wall stress was measured using sonomicrometry. Volume expansion by 30% of blood volume, using donor blood, caused a small increase in right and left atrial diastolic and systolic wall stress but did not significantly increase plasma ANF. Pacing the heart at 6 Hz caused increases in systolic but not diastolic wall stress and caused a significant increase in plasma ANF; the increase was larger after volume expansion. There were no significant differences between the responses of the experimental and control groups. It is concluded that mild hypertension, in the rabbit, does not lead to changes in atrial wall stress or either basal or stimulated release of ANF.     

Physiological concentrations of atrial natriuretic factor stimulate human erythroid progenitors in vitro

Human alpha-ANF[1-28] potentiated erythroid colony formation up to four-fold in cultures containing erythropoietin. Both early and late erythroid precursor cells responded to alpha-ANF[1-28] [0.032 to 1 nM] in a dose dependent fashion. Removal of T lymphocytes and macrophages which have been shown to modulate erythropoiesis did not abolish the stimulatory effect. All major circulatory forms of ANF (alpha-ANF[1-28], alpha-ANF[4-28] and alpha-ANF[5-28]) had potent erythropoietic activity. These results indicate that concentrations of ANF reached during hypoxia stimulate erythroid progenitor cells in the presence of erythropoietin.     

Plasma and urinary clearance rates of atrial natriuretic factor during ontogeny in sheep

The present study was designed to determine the plasma clearance rate of atrial natriuretic factor (ANF) during development in chronically-instrumented fetal, newborn and adult non-pregnant sheep. To determine the contribution of the kidney in the metabolism of ANF, urinary clearance of ANF was also measured. Intravenous infusion of ANF (0.025 and 0.1 microgram.min-1.kg-1) produced a significant decrease in mean arterial blood pressure in newborn lambs and in adult non-pregnant sheep. Estimated plasma ANF clearance rate for the 0.025 and 0.1 microgram.min-1.kg-1 ANF infusion rate were respectively 177 +/- 55 and 155 +/- 34 ml.min-1.kg-1 in fetuses, 138 +/- 26 and 97 +/- 13 ml.min-1.kg-1 in newborn lambs and, 148 +/- 33 and 103 +/- 25 ml.min-1.kg-1 in adult nonpregnant ewes. Fetal, newborn and adult ANF plasma clearance rates during high ANF infusion rate (0.1 microgram.min-1.kg-1) were not significantly different. Low or high ANF infusion rate was not associated with significant changes in urinary ANF concentration or urinary ANF excretion rate. Taken together, the present study demonstrates that ANF plasma clearance rate is similar in fetal, newborn and adult non-pregnant sheep and that the excretory function of the kidney contributes only minimally to ANF plasma clearance rate.     

Effect of human atrial natriuretic peptide on blood pressure after sodium depletion in essential hypertension.

Human atrial natriuretic peptide was infused over four hours in three patients with essential hypertension. When the patients had a sodium intake of 200 mmol (mEq) daily an infusion of 0.5 micrograms atrial natriuretic peptide/min caused no significant change in blood pressure, whereas an infusion of 1.0 micrograms/min caused a gradual decrease in blood pressure and an increase in heart rate. After two to three hours of infusion with the higher dose two patients showed a sudden decrease in heart rate, with symptomatic hypotension. When the same patients had an intake of 50 mmol sodium daily their blood pressure was more sensitive to infusion of atrial natriuretic peptide; one patient again developed symptomatic hypotension, this time during an infusion of 0.5 micrograms/min. During all infusions distinct natriuresis occurred irrespective of whether blood pressure was affected. Prolonged, relatively low dose infusions of atrial natriuretic peptide can cause unwanted symptomatic hypotension. The effect on blood pressure is enhanced after sodium depletion, and blood pressure should be monitored carefully during longer infusions of atrial natriuretic peptide in patients with essential hypertension.     

Atrial natriuretic factor in pregnancy and pregnancy-induced hypertension.

In normal pregnancy, cross-sectional clinical data do not consistently show plasma ANF concentration differences between early pregnancy and the nonpregnant state. Sequential data in the baboon (but not in rat) show a significant decrease in plasma ANF concentration and in cardiac filling pressures in early pregnancy. The latter data support the view that pregnancy is an underfill state secondary to a primary vasodilatation. Cross-sectional and longitudinal studies in normal pregnancy in humans show that plasma ANF levels tend rise to values that are, in the third trimester, higher than in the nonpregnant state. However, late postpartum sequential data (1.5-3 months) in humans do now show a significant drop in plasma ANF concentrations, suggesting that plasma ANF is not actually increased in normal pregnancy. In the baboon (but not in the rat) there is a steady rise in plasma ANF levels to values that are significantly higher in third trimester than before pregnancy. These data suggest that in human pregnancy, in contrast with the baboon, the plasma volume expansion induced by normal pregnancy is not sensed as such by the atria probably because of an isopressive adaptation of plasma volume to an enlarged vascular bed. However, acute decrease or increase of venous return induced by low sodium diet, changing position or infusion of isotonic saline are sensed as such by the atria in normal pregnancy as in the nonpregnant state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma dehydroepiandrosterone sulfate concentration in essential hypertension.

Plasma dehydroepiandrosterone sulfate (DS) concentration has previously been reported to be elevated in hypertensive Japanese men with uncharacterized renin status. Indirect evidence suggests that some patients with low renin essential hypertension might be expected to have an elevated plasma DS concentration. The intravenous furosemide test was utilized to categorize renin status in black and white, male and female hypertensive patients, and plasma DS concentration was measured. Plasma DS concentration in the low and normal renin subgroups did not differ significantly. In addition, no difference in plasma DS concentration was noted between black and white hypertensive patients and normal subjects, though plasma DS concentration decreased with age and was lower in women. We thus conclude that plasma DS concentration is normal in the great majority of patients with essential hypertension.     

Blood-brain barrier and atrial natriuretic factor

In brain, binding sites for atrial natriuretic factor (ANF) have been characterized in areas such as circumventricular organs that lack the tight capillary endothelial junctions of the blood-brain barrier and therefore are exposed to circulating peptides. Since atrial natriuretic factor acts directly on vascular endothelium and has been proposed to be actively involved in blood pressure regulation and fluid homeostasis, it is interesting to know whether ANF receptors exist on brain capillaries that constitute the blood-brain barrier and participate in the constant fluid exchange between blood and brain. The present paper reports recent evidence of the presence of ANF receptors located on the structure. It assesses the specific binding of 125I-labelled ANF on bovine brain microvessel preparations and its coupling with a guanylate cyclase system. The potential physiological role of ANF on brain microcirculation and blood-brain barrier functions is discussed.     

Renal hemodynamic and natriuretic effects of atrial natriuretic factor

In this article we review the renal hemodynamic and excretory actions of atrial natriuretic factor (ANF) and consider some of the mechanisms of its vascular and natriuretic effects. ANF leads to a marked, sustained, and parallel increase in whole-organ and superficial single-nephron glomerular filtration rate (GFR) while mean blood pressure is decreased and renal blood flow (RBF) is unchanged or even decreased. The increase in GFR is caused by an efferent arteriolar vasoconstriction or by a combination of afferent vasodilation and efferent vasoconstriction. ANF also leads to a decrease in the hypertonicity of the innermedullary interstitium. Together with the increase in GFR, this phenomenon accounts wholly or in great part for the ANF-induced natriuresis. The overall renal vascular effects of ANF are complex and may tentatively be conceptualized as a behavior of a functional partial agonist: slight vasoconstriction in vasodilated kidneys, no sustained effects on the vascular resistance in normal kidneys, and vasodilation in vasoconstricted kidneys. The vasoconstrictor effect of ANF may be direct or indirect and depends on extracellular calcium whereas the antagonist effect likely results from alterations in intracellular calcium homeostasis. The data raise the perspective that ANF is not only a powerful natriuretic substance but has the potential of being an important modulator of GFR and RBF in intact animals.     

Rat atrial natriuretic factor. Purification and vasorelaxant activity

The atrial natriuretic activity of rat heart has been found to exist in multiple forms. One of these factors has been purified to apparent homogeneity by a combination of gel filtration and high pressure liquid chromatography in two different systems and its amino acid composition determined. The purified active peptide is shown to have a molecular weight of approximately 3800. In addition, the vasorelaxant activity of rat atrium has been purified and found to cochromatograph with the natriuretic activity in all chromatographic systems employed. Thus, the vasorelaxant activity resides in the natriuretic factor. The existence of this new multifunctional peptide implies a higher level of complexity for cardiovascular control of blood volume and pressure.     

Endogenous platelet-activating factor and anti-platelet-activating factor in patients with renovascular hypertension

Renovascular hypertension is relieved by percutaneous transluminal renal angioplasty. In four patients with renovascular hypertension, platelet-activating factor (PAF) was found to be released into the ipsilateral renal venous blood after percutaneous transluminal renal angioplasty, but was not found in the contralateral renal venous blood following this procedure. Anti-platelet-activating factor with a lipid-like property was also found, and its polarity was slightly lower than that of PAF judging by its behavior on thin layer chromatography. Anti-platelet-activating factor completely blocked the aggregation of rabbit platelets induced by PAF, ADP or arachidonic acid. These results indicate that PAF and anti-platelet-activating factor are released into renal venous blood following percutaneous transluminal renal angioplasty in patients with renovascular hypertension.     

A decade of atrial natriuretic factor research.

Present views on the biological significance of atrial natriuretic factor (ANF) relate this polypeptide hormone to the regulation of blood pressure and volume through its modulating effects on renal function, on blood vessel tone and permeability, and on the renin-angiotensin-aldosterone system. Although very important advances in the understanding of ANF have been made over the decade since its discovery, some fundamental facts about ANF biosynthesis and release remain to be elucidated. Stretch-induced enhancement of ANF release appears as the most significant mechanism underlying the endocrine response of the atria to acute volume load. This response decays over a period of minutes, indicating that chronic stimulation of ANF release involves mechanisms different from, or in addition to, those acting during acute stretch-stimulated release. In neither acute nor chronic conditions are the cellular or molecular mechanisms underlying ANF release understood. To better understand long-term stimulation of ANF release, we have conducted extensive in vitro testing of several hormones and neurotransmitters to determine their ability to modify ANF release. From these studies, clear-cut evidence of ANF stimulation was obtained with the vasopressor peptide endothelin. Investigations on the cell and molecular biology of cardiac muscle development and hypertrophy have shown that ANF is involved in cardiac growth. The role played by ANF in these processes is now being determined, but this is one line of evidence that suggests that this hormone, together with other natriuretic peptides, may have autocrine or paracrine functions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma vasopressin and atrial natriuretic factor in response to blood volume changes in the anaesthetized rabbit

The influence of aortic baroreceptors and vagal afferent nerves on the release of immunoreactive vasopressin (iVP) and immunoreactive atrial natriuretic factor (iANF) was examined in anaesthetized rabbits. Changes in plasma concentrations of iVP and iANF, heart rate, mean arterial pressure, and right atrial pressure were measured in response to blood volume changes (+20, +10, -10, -20%). Carotid sinus pressure was maintained at 100 mmHg (1 mmHg = 133.3 Pa), and blood volume changes were performed before and after bilateral vagotomy (VNX) in all experiments. Two experimental groups were studied: rabbits with aortic depressor nerves intact (ADNI) and those with aortic depressor nerves sectioned (ADNX). Mean arterial and right atrial pressures decreased during haemorrhage and increased in response to volume expansion. Plasma iVP concentrations increased with haemorrhage and decreased with volume expansion in the ADNI group. Plasma iANF, however, decreased with haemorrhage and increased during volume expansion in both ADNI and ADNX groups. Vagotomy caused an increase in baseline plasma iANF in the ADNX group. The responses of iANF to blood volume changes were augmented after VNX and ADNX. The results show that neither the aortic baroreceptor nor the vagal afferent input are needed for the iANF response to changes in blood volume, over the range of +/- 20%. In contrast, intact aortic baroreceptors are essential for changes in circulating iVP in this preparation.     

Atrial dynamics and release of atrial natriuretic factor in vivo.

In anaesthetized rabbits blood volume was altered by infusion and withdrawal of donor blood over the range of +60 to -40% of the blood volume. Right and left atrial pressures were measured and it was shown that sonomicrometry allowed adequate measurement of phasic changes in atrial dimensions. Plasma immunoreactive atrial natriuretic peptide concentration changed in a nonlinear fashion with changes in blood volume, and was linearly related to both peak systolic and peak diastolic right and left atrial wall stress. It was not possible to make the distinction between distension (diastolic stress) or tension (systolic stress) as the major determinant of ANF release in response to changes in blood volume.