Atrial Natriuretic Factor Prohormone Research Articles

Release of atrial natriuretic factor prohormone peptides 1-30, 31-67 and 99-126 from freshwater- and seawater-acclimated perfused trout (Oncorhynchus mykiss) hearts

Atrial natriuretic factor (ANF), a 28-amino-acid peptide hormone produced in the heart, circulates in both freshwater and seawater rainbow trout. In mammals, two other peptide hormones, proANF 1-30 and proANF 31-67, derived from the same 126-amino-acid prohormone as ANF (amino acids 99&shyp;126), circulate and have natriuretic and diuretic properties. It has never been determined whether these peptides circulate in fish. The present investigation was designed to determine (1) whether proANF 1-30 and/or proANF 31-67 circulate in perfused hearts from freshwater- and seawater-acclimated rainbow trout (Oncorhynchus mykiss) in situ, and (2) if they do, to determine whether increasing the filling pressure of the heart causes their release in trout as it does in mammals. High-performance gel-permeation chromatography of fish plasma revealed that both proANF 1-30 and 31-67 circulate in freshwater- and seawater-acclimated trout plasma at threefold higher concentrations than does ANF. The basal rates of release of ANF and proANF 1-30 and 31-67 were similar in both freshwater and seawater trout, with the rate of release of proANF 1-30 being 10 times higher and that of proANF 31-67 20 times higher than that of ANF. When the filling pressure was increased to the peak of the Starling curve (max), the rate of release of ANF and proANFs 1-30 and 31-67 increased fivefold for each peptide in the freshwater trout, while in seawater trout the rates of release increased six- to ninefold. We conclude that proANF 1-30 and 31-67, as well as ANF, circulate in both freshwater-and seawater-acclimated trout and do so at concentrations higher than that of ANF. Increasing the filling pressure to the trout heart was found to cause a similar increase in the release rates for each of these peptides, but the maximal increase was higher in the seawater-acclimated trout, apparently because they showed a larger increase in cardiac output.

Plasma-circulating levels of natriuretic peptides in patients with bone and soft tissue injuries

To evaluate the release and possible role of N-terminal end of atrial natriuretic factor (ANF) prohormone (proANF-1–30) and C-terminal end of ANF prohormone ( aANP-1–28) in patients with soft tissue and bone injuries, 20 patients with soft tissue injuries, 18 bone-fractured patients, and 21 healthy controls were examined. Samples were collected from patients within 24 h after injury. Plasma level of proANF-1–30 and aANP-1–28 were higher in orthopedic patients than the soft tissue injury patients compared to controls ( P < 0.005, P < 0.05, respectively). proANF-1–30 was over 15-fold greater than aANP-1–28 in the healthy control samples. These data hypothesized that the concentration of proANF-1–30 may be related to tissue damages in man.

Modulation of Renin Secretion by A trial Natriuretic Factor Prohormone Fragment 31–67

Background: Earlier studies have indicated that the atrial natriuretic factor prohormone fragment 31-67 (Pro ANF31–67) has important effects for the promotion of sodium excretion and vasodilation in several animal species. However, the mechanisms for the natriuretic actions of Pro ANF31–67 are not completely defined. In the present study, the effects of synthetic Pro ANF31–67 on renin secretion were examined in sodium-depleted, anesthetized dogs with a single intact kidney (n = 5). Methods: After 3 20-minute control renal clearance periods, synthetic dog Pro ANF31–67 was given intrarenally at a sustained dose of 0.03 μg/kg/min for 3 20-minute experimental intervals, and after discontinuation of the peptide infusion, 3 final 20-minute recovery periods were determined. Results: Sustained intrarenal infusions of the Pro ANF31–67 produced striking decrements (p<0.05) in renin secretion, from a control value of 1418 ± 243 to 401 ± 223 ng of angiotensin l/min. This 66% fall in renin secretion was associated with significant (P < 0.05) increases in creatinine clearance (40%), renal blood flow (8%), urine flow (50%), and sodium excretion (17%). Conclusions: It is suggested that this inhibition of renin secretion was mediated, at least in part, in response to a ProANF31–67-induced increment in the sodium load delivered to the macula densa. An interaction of the peptide with the renal vascular receptor for suppression of renin release is also possible. ProANF31–67 may represent an important hormonal mechanism involved in the regulation of body-fluid balance.

Modulation of renin secretion by atrial natriuretic factor prohormone fragment 31-67.

Earlier studies have indicated that the atrial natriuretic factor prohormone fragment 31-67 (Pro ANF31-67) has important effects for the promotion of sodium excretion and vasodilation in several animal species. However, the mechanisms for the natriuretic actions of Pro ANF31-67 are not completely defined. In the present study, the effects of synthetic Pro ANF31-67 on renin secretion were examined in sodium-depleted, anesthetized dogs with a single intact kidney (n = 5). After 3 20-minute control renal clearance periods, synthetic dog Pro ANF31-67 was given intrarenally at a sustained dose of 0.03 microg/kg/min for 3 20-minute experimental intervals, and after discontinuation of the peptide infusion, 3 final 20-minute recovery periods were determined. Sustained intrarenal infusions of the Pro ANF31-67 produced striking decrements (p<0.05) in renin secretion, from a control value of 1418 +/- 243 to 401 +/- 223 ng of angiotensin I/min. This 66% fall in renin secretion was associated with significant (P < 0.05) increases in creatinine clearance (40%), renal blood flow (8%), urine flow (50%), and sodium excretion (17%). It is suggested that this inhibition of renin secretion was mediated, at least in part, in response to a ProANF31-67-induced increment in the sodium load delivered to the macula densa. An interaction of the peptide with the renal vascular receptor for suppression of renin release is also possible. ProANF31-67 may represent an important hormonal mechanism involved in the regulation of body-fluid balance.

Hemodynamic and renal effects of ProANF31-67 in hypertensive rats.

It has been demonstrated previously that the atrial natriuretic factor prohormone fragment 31-67 (ProANF31-67) circulates in animals and possesses natriuretic and vasodilating actions. Although the plasma levels of the peptide are reportedly elevated in patients with high blood pressure, its role and actions in hypertension are unknown. In the present study, synthetic human ProANF31-67 was infused intravenously at doses of 0, 10, 30, and 100 ng/kg/min into respective groups of anesthetized normotensive and spontaneously hypertensive rats. Mean arterial pressure (MAP), urine flow rate (UV), and sodium excretion (UNaV) were measured during two consecutive 30-min periods. In both strains of rats, reductions in MAP with ProANF31-67 were similar in magnitude and dose-related. Sodium excretion responses to the peptide infusions also were remarkably similar in both normotensive and hypertensive rats, and the responses demonstrated 3- to 5-fold (P < 0.05) increments compared to control at the doses of 10 and 30 ng/kg/min. However, in the two strains of rats, attenuation of natriuresis occurred with the highest infusion dose of 100 ng/kg/min and was probably related to the large decreases in MAP of 17-23 mmHg at this dose of the peptide. The present results indicate the ProANF31-67 has important hemodynamic and renal effects in hypertension and may represent one compensatory mechanism involved in this disease.

N-terminal proANF in acute atrial fibrillation: A biochemical marker of atrial pressures but not a predictor for conversion to sinus rhythm

Background: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF. Methods: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate. Results: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters. Conclusion: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters. (Am Heart J 1998;135:1040-7.)

Changes in blood pressure and in vasoactive and volume regulatory hormones during semistarvation in obese subjects

The mechanisms underlying the reduction in blood pressure that occurs with a severe energy-restricted diet were evaluated in 12 obese subjects during 8 days on a very—low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium per day. The relationship between changes in blood pressure, sodium balance, plasma volume, renin-aldosterone and sympathetic nervous system activities, plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF) prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1) concentrations was investigated. A negative sodium balance was present throughout the diet and was associated with a moderate reduction in plasma volume, a marked activation of the renin-aldosterone system, and a concomitant reduction in C- and N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal proANF and ANF secretion documented before the diet, disappeared after 8 days of dieting, in contrast to a greater postural stimulation of aldosterone and renin. A negative correlation was found between the changes of C- and N-terminal ANF prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP, and ET-1 remained unchanged. These results indicate that the decrease in blood pressure occurring during severe caloric restriction was essentially due to the reduction in the effective blood volume, as reflected by the stimulation of the renin-aldosterone system and the decrease in ANF levels. The lack of any changes in catecholamine excretion and endothelin levels suggests that peripheral vascular resistance did not change significantly in these circumstances.

ANF system in the newborn piglet pulmonary vessels.

The atrial natriuretic factor (ANF) induces diuresis, natriuresis, and vasodilation. Although it was originally found to be secreted from the atria, ANF synthesis has been demonstrated in other organs. The adult lung is not only the first target organ for ANF, but it also expresses the ANF gene and synthesizes, releases, and clears ANF from the circulation. We have shown the presence of ANF in human fetal lungs and also demonstrated that these lungs can release bioactive ANF. However, the role of the ANF system in the newborn lung is unknown. Therefore we studied the ANF system in pulmonary vessels (arteries and veins dissected from the hilum down to a 100-microm diameter), in isolated perfused lungs, and in the plasma from pulmonary artery and vein of 1- and 7-day-old piglets. High-performance liquid chromatography (HPLC) revealed the presence of both the mature peptide and the ANF prohormone in pulmonary vein microsomes, but in pulmonary arteries, only the mature form was identified. Furthermore, in the veins, the ANF content tended to be higher in 7- than in 1-day-olds. ANF caused a dose-dependent decrease in perfusion pressure (p < 0.05). In veins and arteries, most of the ANF receptors were of the type A guanylate cyclase as opposed to clearance receptors. Interestingly, the ANF receptors were fewer in veins, where synthesis takes place, than in arteries (p < 0.05). Significant circulating ANF plasma levels were measured by radioimmunoassay in both pulmonary artery and vein. However, there was no site difference in ANF plasma levels, suggesting that ANF is cleared and synthesized in the pulmonary vessels. In conclusion, the entire ANF system is present in the newborn piglet pulmonary vessels. The paucity of clearance receptors compared with functional receptors potentiates the role of ANF in the regulation of postnatal pulmonary vascular resistance.

Release of atrial natriuretic factor prohormone peptides 1-30, 31-67 and 99-126 from freshwater- and seawater-acclimated perfused trout (Oncorhynchus mykiss) hearts

Atrial natriuretic factor (ANF), a 28-amino-acid peptide hormone produced in the heart, circulates in both freshwater and seawater rainbow trout. In mammals, two other peptide hormones, proANF 1-30 and proANF 31-67, derived from the same 126-amino-acid prohormone as ANF (amino acids 99&shyp;126), circulate and have natriuretic and diuretic properties. It has never been determined whether these peptides circulate in fish. The present investigation was designed to determine (1) whether proANF 1-30 and/or proANF 31-67 circulate in perfused hearts from freshwater- and seawater-acclimated rainbow trout (Oncorhynchus mykiss) in situ, and (2) if they do, to determine whether increasing the filling pressure of the heart causes their release in trout as it does in mammals. High-performance gel-permeation chromatography of fish plasma revealed that both proANF 1-30 and 31-67 circulate in freshwater- and seawater-acclimated trout plasma at threefold higher concentrations than does ANF. The basal rates of release of ANF and proANF 1-30 and 31-67 were similar in both freshwater and seawater trout, with the rate of release of proANF 1-30 being 10 times higher and that of proANF 31-67 20 times higher than that of ANF. When the filling pressure was increased to the peak of the Starling curve (max), the rate of release of ANF and proANFs 1-30 and 31-67 increased fivefold for each peptide in the freshwater trout, while in seawater trout the rates of release increased six- to ninefold. We conclude that proANF 1-30 and 31-67, as well as ANF, circulate in both freshwater-and seawater-acclimated trout and do so at concentrations higher than that of ANF. Increasing the filling pressure to the trout heart was found to cause a similar increase in the release rates for each of these peptides, but the maximal increase was higher in the seawater-acclimated trout, apparently because they showed a larger increase in cardiac output.

Serum N-terminal proatrial natriuretic factor in children with congenital heart disease.

An objective and simple method of establishing and grading heart failure in children is needed. The N-terminal of the atrial natriuretic factor prohormone, called proANF, is stable in vitro, relatively easy to measure and has been demonstrated as a clinically useful marker of heart failure in adults. We measured proANF in 62 children with congenital heart disease and in 62 age-matched controls, in order to examine the relationship of proANF to different clinical and haemodynamic parameters. Echo Doppler cardiography was performed in all children, and 29 also underwent cardiac catheterization. The children were classified for volume and pressure load in each cardiac chamber, for shunt size and for signs of heart failure. In paediatric patients without cardiac or renal disease, median proANF was 384 pmol.l(-1). In children with congenital heart disease, median proANF was 904 (200-5320) pmol.l(-1) (P < 0.001). The three groups with the highest proANF levels were children with documented high atrial pressure (median proANF 1885 pmol.l(-1)), a large left to right shunt (median proANF 1565 pmol.l-(1)) and moderate or severe heart failure (median proANF 1305 pmol.l(-1)). Furthermore, the proANF level correlated negatively with age and glomerular filtration rate. We conclude that elevation of the proANF level is related to atrial pressures, heart failure and a high pulmonary to systemic flow ratio. These findings make proANF a potential new diagnostic tool in heart disease in children.

Circadian relationships between circulating atrial natriuretic peptides and serum calcium and phosphate in healthy humans

Long-acting natriuretic peptide (LANP), vessel dilator (VSDL), and atrial natriuretic factor (ANF) consisting of amino acids (aa) 1 to 30, 31 to 67, and 99 to 126, respectively, of the 126-aa ANF prohormone circulate in humans. Among the biologic properties of these peptides is the ability of ANF to decrease intracellular calcium concentrations. To determine if atrial natriuretic peptides are directly related to serum calcium and/or phosphate in healthy normocalcemic humans, we examined 21 24-hour profiles of VSDL, LANP, ANF, and serum calcium and phosphate in 14 healthy humans. VSDL, LANP, and ANF each had significant ( P < .001) circadian rhythms, with peak concentrations late during sleep (at 4:00 AM) being nearly twice the concentrations in the afternoon and evening. Serum calcium and phosphate also had significant circadian rhythms ( P < .001) with troughs nearly opposite to those of the atrial natriuretic peptides, suggesting that atrial peptides may be important in the modulation of the circadian rhythms of calcium and phosphate. The nearly identical circadian rhythms of the atrial natriuretic peptides and of parathyroid hormone (PTH) reported by others, along with evidence that PTH may increase atrial peptide release, suggest that some of the effects attributed to PTH may be mediated by atrial natriuretic peptides.

Atrial Natriuretic Factor (ANF) Prohormone Accumulates in the IgG Fraction of Anti-ANF Hybridoma-Bearing Mice

We demonstrate immunoreactive mouse atrial natriuretic factor (ANF) in the IgG fraction prepared from ascites or serum of mice bearing an anti-rat ANFArg101-Tyr126hybridoma. The HPLC profile of the ANF demonstrates that the IgG fraction contains both mature ANFSer99-Tyr126and the prohormone ANFAsn1-Tyr126. The presence of circulating prohormone in the hybridoma-bearing mice is not secondary to changes in fluid volume due to ascites formation. The anti-ANF antibody appears to protect the ANFAsn1-Tyr126from both maturation and rapid receptor-mediated clearance. Our results suggest, therefore, that the ANFAsn1-Tyr126can be secreted into a compartment that is accessible to antibody and that maturation of the ANF prohormone may be an extracellular event.

Circadian relationships between circulating atrial natriuretic peptides and serum sodium and chloride in healthy humans.

Long-acting natriuretic peptide (LANP), vessel dilator (VSDL), and atrial natriuretic factor (ANF) consisting of amino acids 1-30, 31-67, and 99-126 of the 126 amino acid ANF prohormone, respectively, circulate in humans and have potent natriuretic properties. To determine whether these peptides have a direct relationship to serum Na and/or Cl, we examined 21 24-hour profiles of these peptides and Na and Cl in 14 healthy humans. LANP, VSDL, ANF, and Cl had significant (p < 0.001) circadian rhythms with peak concentrations at 04.00 h. The circadian rhythm of serum Na was exactly opposite. Sodium correlated negatively with LANP (p = 0.021) and ANF (p = 0.007), while Cl correlated positively with LANP (p = 0.003) and VSDL (p = 0.001). These data suggest that the atrial peptides may be important for the maintenance of serum Na and Cl within their normal ranges and in the modulation of their daily circadian rhythms.

Atrial Natriuretic Peptide Gene Expression within Invertebrate Hearts

The present investigation was designed to (1) determine if atrial natriuretic factor gene expression occurs within invertebrates as well as within vertebrates; (2) determine whether the product of this gene expression is the 126-amino-acid atrial natriuretic factor prohormone or some other molecular species; and (3) evaluate within the same invertebrates if the products of atrial natriuretic factor gene expression are released into their circulation. Utilizing a very sensitive RNase protection assay it was found that atrial natriuretic peptide gene expression occurs within the heart of the oyster, Crassostrea virginica, and within the heart of the blue crab, Callinectes sapidus , but was expressed sevenfold less than in a vertebrate heart (i.e. rat, Rattus norvegiucs). High-performance gel-permeation chromatography followed by N-terminal and C-terminal atrial natriuretic factor prohormone radioimmunoassays indicated that the molecular species synthesized within the oyster and blue crab hearts was the atrial natriuretic factor prohormone. The product(s) of this atrial natriuretic factor gene expression (i.e., atrial natriuretic peptides) was found to be released into the circulation, i.e., hemolymph, of both the oyster and the blue crab.

Atrial Natriuretic Peptides and Cyclic Guanosine Monophosphate Metabolism

Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126 amino acid ANF prohormone, increases cyclic guanosine monophosphate (GMP) (thought to be the mediator of its physiologic effects) in plasma and urine of human subjects. Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide, consisting of amino acid 1-30, 31-67, and 79-98, respectively, of this same prohormone have natriuretic, diuretic, kaliuretic, and blood pressure lowering properties in humans. These three new peptide hormones increase cyclic GMP in vitro but were never investigated to determine whether they also cause extrusion of cyclic GMP from cells, resulting in an increase of cyclic GMP in plasma and/or urine. Infusion of each of these peptide hormones at their 100 ng/kg body weight/min concentrations for 60 minutes into healthy humans resulted in a sevenfold increase in cyclic GMP in plasma and urine secondary to ANF, but no significant increase secondary to the other atrial peptide hormones. Based on the current data, ANF has a unique effect on the metabolism of cyclic GMP, causing it to be extruded from the cell, whereas the other three atrial peptides represent the more classical metabolism of cyclic GMP via cyclic GMP phophodiesterases.

Kaliuretic peptide and long acting natriuretic peptide as well as atrial natriuretic factor inhibit aldosterone secretion

The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1-30 (long acting natriuretic peptide), 31-67 (vessel dilator) and 79-98 (kaliuretic peptide) as well as 99-126 (atrial natriuretic factor (ANF)) of the 126 amino acid ANF prohormone inhibit aldosterone secretion. Thirty healthy human subjects were studied following infusion of 100 ng/kg body weight/min for 60 min of each of the respective peptides. Kaliuretic peptide decreased plasma aldosterone concentration by the greatest amount (6-fold) and plasma aldosterone was still significantly decreased (P < 0.001) three hours after stopping the infusion. In contrast, within 30 min of cessation of the ANF infusion, plasma aldosterone levels had returned to pre-infusion values. Long acting natriuretic peptide also significantly (P < 0.01) decreased plasma aldosterone levels which remained significantly (P < 0.001) decreased 3 h after cessation of infusion. Vessel dilator did not decrease plasma aldosterone levels. Kaliuretic peptide, ANF and long acting natriuretic peptide also decreased (P < 0.01) urinary aldosterone concentrations. None of these peptides changed the plasma potassium concentration. We conclude that two new peptide hormones (long acting natriuretic peptide and kaliuretic peptide) inhibit aldosterone secretion. The length of time that aldosterone secretion is inhibited following kaliuretic peptide and long acting natriuretic peptide infusion is significantly longer (P < 0.001) than following ANF infusion.

Release of kaliuretic peptide during immersion-induced central hypervolemia in healthy humans.

Kaliuretic peptide, a new peptide hormone consisting of amino acids 79-98 of the 126 amino acid atrial natriuretic factor (ANF) prohormone, is synthesized in the heart and is a potent stimulator of potassium excretion. The mechanism(s) controlling the release of kaliuretic peptide heretofore has not been defined. Because water immersion to the neck provides an acute central volume expansion identical to that produced by 2 liters of saline but without the plasma compositional change, immersion to the neck (NI) was utilized to assess kaliuretic peptide responses to acute central blood volume expansion in seven seated sodium-replete normal subjects. Since atrial natriuretic factor (ANF; amino acids 99-126 of the prohormone) originates from the amino acids adjacent to kaliuretic peptide in the ANF prohormone but is proteolytically cleaved from the rest of the prohormone before release, measurement of ANF was incorporated into this study to determine if there are differences with respect to release of these two portions of the ANF prohormone. Both kaliuretic peptide and ANF increased promptly with NI, with ANF peaking at 1 hr of immersion, whereas kaliuretic peptide peaked at the 3rd hr of immersion. With cessation of immersion, ANF decreased to preimmersion levels within 0.5 hr while kaliuretic peptide was still significantly (P < 0.05) elevated at 1 hr postimmersion. These findings indicate that kaliuretic peptide and ANF are released simultaneously but that kaliuretic peptide peak circulating concentration and its return to preimmersion values are prolonged compared with ANF. These last findings suggest a slower clearance from the circulation for kaliuretic peptide. The diuretic peak response to NI corresponded in a temporal manner to the peak circulating concentration of kaliuretic peptide, suggesting a possible physiologic role for kaliuretic peptide in modulating volume homeostasis in humans.

Blood pressure and atrial natriuretic peptides correlate throughout the day

Vessel dilator consisting of amino acids (a.a.) 31–67 and atrial natriuretic factor (ANF) composed of a.a. 99–126 of the 126 a.a. ANF prohormone circulate in humans and have potent vasodilatory properties. To determine whether these atrial natriuretic peptides are directly related to blood pressure in healthy normotensive humans, we recently had the unique opportunity to examine the circadian rhythms of vessel dilator, ANF, and blood pressure in seven individuals in 1988 and again in 1993. The changes in mean arterial pressure and systolic and diastolic blood pressure in these individuals during this 5-year hiatus allows comparison in the same individual, if circulating concentrations of atrial natriuretic peptides directly correlate with naturally occurring changes in blood pressure. In both 1988 and in 1993 vessel dilator and ANF each had significant ( p < 0.001) circadian rhythms with their peak concentrations at 4:00 Ann being nearly twice their concentrations at 4:00 PM. Mean arterial pressure, systolic blood pressure, and diastolic blood pressure also had significant circadian rhythms with peaks and troughs that were exactly opposite to those of ANF and vessel dilator. A significant inverse correlation between 24-hour averages of mean arterial blood pressure and 24-hour averages of vessel dilator ( p - 0.05) and ANF ( p = 0.02) was also found. These data suggest that vessel dilator and ANF are important for the maintenance of blood pressure within the normotensive range.

Effects of ANF prohormone peptides in conscious primates.

1. Recent studies suggest that amino-terminal peptides from the atrial natriuretic factor (ANF) prohormone are natriuretic. 2. The effects of pro ANF 31-67 and ANF 99-126 on renal function were studied in conscious non-human primates (Macaca fascicularis). 3. Results show that pro ANF 31-67 and ANF 99-126 are diuretic and natriuretic and that when the two peptides are given in combination sodium excretion increases in an additive fashion. 4. These results indicate that multiple peptides from the ANF prohormone are natriuretic. Furthermore, these findings suggest that the combined action of these peptides causes the natriuresis that occurs after the release of endogenous atrial peptides.

Secretion and renal effects of ANF prohormone peptides.

1. Atrial natriuretic factor (ANF) and pro ANF peptide appears to be secreted simultaneously from the atria in response to atrial stretch. 2. The major peptide forms secreted from rat atria appear to be ANF (pro ANF 99-126) as the primary C-terminal peptide and pro ANF 1-30 as the primary N-terminal peptide, as opposed to 1-67 or 1-98. 3. The plasma concentrations of ANF and pro ANF 1-30 are increased by acute stimulation with blood volume expansion and the plasma levels of ANF and N-terminal ANF prohormone peptides are chronically elevated by high salt diet. 4. Pro ANF 31-67 produces a natriuresis which is not dependent on an increase in renal cGMP excretion, decreases in plasma renin activity (PRA) or elevations in plasma ANF concentration.