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Biomedical subjects

D L Vesely

Publications and source records attributed to D L Vesely.

At least 19 recordsLinked to original sources

Peptides from the N-terminus of the atrial natriuretic factor prohormone enhance guanylate cyclase activity and increase cyclic GMP levels in a wide variety of tissues.

The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor (ANF) prohormone contains three peptides consisting of a.a. 1-30 (proANF 1-30), a.a. 31-67 (proANF 31-67) and a.a. 79-98 (proANF 79-98) with blood pressure lowering, sodium and/or potassium excreting properties similar to atrial natriuretic factor (a.a. 99-126, C-terminus of prohormone). ProANF 1-30 and proANF 31-67 have separate and distinct receptors from ANF in both vasculature and in the kidney to help mediate the above effects. At the cellular level proANFs 1-30, 31-67, and 79-98 as well as ANF's effects are mediated by enhancement of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system in vasculature and in the kidney. These peptides from the N-terminus of the ANF prohormone circulate normally in man and in all animal species tested. The object of the present investigation was to determine if these peptides have the ability to enhance either guanylate cyclase and/or adenylate cyclase in a variety of other tissues in addition to kidney and vasculature. ProANF 1-30, proANF 31-67, proANF 79-98, and ANF all increased rat lung, liver, heart and testes, but not spleen, particulate guanylate cyclase 2- to 3-fold at their 100 nM concentrations. Dose response curves revealed that maximal stimulation of particulate guanylate cyclase activity by these newly discovered peptides was at their 1 microM concentrations, with no further increase in activity above their 1 microM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pharmacokinetic characterization of the postdistribution phase of prohormone atrial natriuretic peptides amino acids 1-98, 31-67, and atrial natriuretic factor during and after rapid right ventricular pacing in dogs.

Release rate constants and disappearance rate constants were determined for three atrial natriuretic peptides consisting of amino acids 1-98 (i.e., proANF 1-98), the midportion of the ANF prohormone consisting of amino acids 31-67 (i.e., proANF 31-67) and amino acids 99-126 (i.e., ANF) after right ventricular pacing at 100, 125, 150, and 180 bpm in six male mongrel dogs. Right atrial and femoral vein blood was obtained at baseline, and at 5, 12, 19, 26, 56, 86, 116, 146, and 206 minutes after right ventricular pacing. Resulting plasma concentration-time data derived parameters were compared. The disappearance rate constants for atrial and femoral venous proANF 1-98 were 0.0144 +/- 0.0087 (X +/- SD) and 0.0175 +/- 0.0075 min-1, respectively (t = 0.6158) and release rate constants were 0.1569 +/- 0.1504 and 0.0670 +/- 0.0393 min-1, respectively (t = 1.8269; P greater than .05). The proANF 31-67 disappearance rate constants were 0.0139 +/- 0.0082 and 0.0148 +/- 0.0132 min-1, respectively (t = 0.1192) and release rate constants were 0.0957 +/- 0.0414 and 0.1984 +/- 0.1762 min-1, respectively (t = 1.4812). The ANF elimination phase disappearance rate constants were 0.0663 +/- 0.0273 and 0.1116 +/- 0.0539 min-1 (t = 2.0923, P greater than .05), respectively, and the release rate constants were 0.1335 +/- 0.0532 and 0.1638 +/- 0.0520 min-1 (t = 0.7878, P greater than .05), respectively. These data indicate that proANF 1-98 and proANF 31-67 circulating beta post-distribution half-lives are approximately 45 minutes whereas beta half-life of ANF is 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The most primitive heart in the animal kingdom contains the atrial natriuretic peptide hormonal system.

1. The newly described atrial natriuretic peptide hormonal system appears to play an important role in the endocrine control of sodium and water metabolism in human and vertebrate animals, but neither atrial natriuretic factor (ANF, C-terminal amino acids (a.a.) 99-126 a.a. prohormone) nor the rest of the ANF prohormone have ever been demonstrated in the heart of an invertebrate. 2. The present investigation was designed to determine whether the earthworm, Lumbricus terrestis, the first animal in the phylogenic tree with any form of heart, has either ANF and/or the 98 a.a. N-terminus of the ANF prohormone. 3. Both an ANF-like peptide (189 +/- 32 ng/g of tissue) and the N-terminus of the ANF prohormone-like peptide (1985 +/- 27 ng/g of tissue) were present in the earthworm heart at concentrations significantly higher (P less than 0.001) than in rat (Rattus norvegicus) heart ventricles. 4. This newly-described hormonal system, thus, appears to be present in a much larger proportion of the animal kingdom than previously thought, including invertebrates as well as vertebrates.

Animals

Immunocytochemical localization of proANF 1-30, proANF 31-67 and atrial natriuretic factor in the kidney.

ProANF [1-30 first 30 amino acids (a.a) of the 126 a.a atrial natriuretic factor (ANF) prohormone], ProANF 31-67 (a.a 31-67) as well as atrial natriuretic factor (a.a 99-126), of the ANF prohormone localized to the sub-brush border of the pars convoluta and pars rectus of the proximal tubules of hydrated and dehydrated rat kidneys with immunoperoxidase staining. Immunofluorescent studies revealed that each of these peptides and especially ProANF 31-67 had a strong predilection for the perinuclear region in the proximal and distal tubules. ProANFs 1-30, 31-67, and 99-126 (that is, ANF) also localized with both immunoperoxidase and immunofluorescent staining to the cortical collecting ducts, glomeruli, peritubular, and interstitial blood vessels. ProANF 31-67 immunoperoxidase staining was particularly striking in the elastica of the small and large interstitial arteries. The whole prohormone being present was suggested by immunological recognition in the rat kidney of both the N-terminus and C-terminus of the ANF prohormone by radioimmunoassays. The concentration of the N-terminus in the kidney was 1.0 +/- 0.03 ng/g of kidney weight, while the C-terminus of the ANF prohormone concentration was 0.4 +/- 0.01 ng/g of kidney tissue. These findings of a sub-brush border and perinuclear location of the N-terminal and C-terminal ANF prohormone peptides suggest that the atrial natriuretic factor prohormone may be synthesized in and/or the respective peptides are captured by the proximal tubules, but also to a lesser extent by the distal tubules of the kidney.

Animals

Weight reduction decreases the circulating concentration of the N-terminus of the ANF prohormone.

The N-terminus of the atrial natriuretic factor (ANF) prohormone (ie, proANF 1-98) contains two vasodilatory peptides consisting of amino acids (aa): aa 1-30 (ie, proANF 1-30) and aa 31-67 (ie, proANF 31-67) of the 126 aa prohormone. The relationship of this N-terminus to the renin-aldosterone axis and blood pressure reduction was investigated in 18 obese subjects (5 hypertensive and 13 normotensive) placed on a 12-week, low sodium (40 mmol), weight reducing diet. The N-terminus of the ANF prohormone and proANF 31-67, which circulates as a distinct entity after being proteolytically cleaved from the N-terminus, were significantly (p less than 0.001) higher (767 +/- 1.01 and 816 +/- 135 fmol/ml) in the obese hypertensive group compared with the obese normotensive group (377 +/- 24 and 356 +/- 17 fmol/ml, respectively) prior to beginning the weight reduction program. There was a dramatic fall in the N-terminus and in proANF 31-67 after 1 week of weight reduction in both obese groups, which correlated with the decrease in mean arterial pressure during the first week and throughout the 12 weeks of weight reduction (r = .54, p less than 0.001 and r = .59, p less than 0.001, respectively). ProANF 1-98 had a significant (p less than 0.01) inverse correlation with plasma renin in both obese groups. ProANF 31-67, likewise, had an inverse correlation with plasma renin in the hypertensive (p less than 0.002), as well as the normotensive (p less than 0.03) subjects. ProANF 31-67 did not significantly correlate with aldosterone in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of changes in sodium intake on atrial natriuretic factor (ANF) and peptides derived from the N terminus of the ANF prohormone in the rat.

The purpose of the present study was to determine whether variations in salt intake would alter the plasma concentrations of atrial natriuretic factor and the N-terminal atrial natriuretic factor prohormone peptides proANF 1-98 and proANF 31-67. Two groups of rats were placed on different salt intakes for 1 week. The low salt group of rats was fed a diet providing less than 0.1 mM NaCl/day and given deionized water to drink. The normal salt group of rats was fed regular rat chow with deionized water to drink, providing them with approximately 2 mM NaCl/day. Plasma atrial natriuretic factor was 204 +/- 60 pg/ml (mean +/- SE) in normal salt rats and was significantly lower in the low salt group (44 +/- 13 pg/ml, P less than 0.01). ProANF 1-98 was also significantly higher in the normal salt group (635 +/- 47 pg/ml) compared with the low salt group (353 +/- 33 pg/ml, P less than 0.01). ProANF 31-67 was 123 +/- 21 pg/ml in the normal salt group and 59 +/- 12 pg/ml in the low salt group (P less than 0.05). Plasma renin activity in ng angiotensin l/ml/hr averaged 1.80 +/- 0.15 in the normal salt group of rats and was significantly higher in the low salt group of rats (5.66 +/- 1.07, P less than 0.05). These results suggest that atrial natriuretic factor and the atrial natriuretic factor prohormones may play a role in the physiological adjustments to low salt intake.

Animals

Atrial natriuretic peptide hormonal system in plants.

To determine if atrial natriuretic peptides are present in plants as well as animals, where they are important for water and sodium metabolism, the leaves and stems of the Florida Beauty (Dracena godseffiana) were examined. The N-terminus consisting of amino acids (a.a.) 1-98 (i.e., pro ANF 1-98), the mid portion of the N-terminus (a.a. 31-67; pro ANF 31-67), and C-terminus (a.a. 99-126; ANF) of the 126 a.a. atrial natriuretic factor (ANF) prohormone were all present in the leaves and stems of this plant. The concentrations of pro ANF 1-98, pro ANF 31-67 and ANF-like peptides of 120 +/- 20, 123 +/- 21, and 129 +/- 20 ng/g of plant tissue in leaves and 109 +/- 20, 96 +/- 21, and 124 +/- 18 ng/g of tissue, respectively, in the stems were lower (P less than 0.05) than their concentrations in rat (Rattus norvegicus) heart atria of 196 +/- 40, 192 +/- 28, and 189 +/- 15 ng/g of tissue respectively, but higher (P less than 0.001) than their respective concentrations of 4.3 +/- 1.4, 4.1 +/- 1.2, and 3.9 +/- 1 ng/g of rat heart ventricular tissue. We conclude that the atrial natriuretic peptide-like hormonal system is present in the plant kingdom as well as in the animal kingdom.

Animals

Exercise increases the circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in normal individuals.

Recently two peptides consisting of amino acids (aa) 1 to 30 and 31 to 67 of the N-terminus of the 126 aa prohormone of atrial natriuretic factor (proANF), as well as atrial natriuretic factor (ANF, aa 99 to 126; C-terminus), were found to have vasodilatory and natriuretic properties. These peptides, as well as ANF, circulate in humans as part of the N-terminus of the prohormone. To determine the effect of graded exercise on the circulating concentrations of the N-terminus and C-terminus of the ANF prohormone in normal persons, 12 healthy individuals (mean age 45 +/- 2 years) were evaluated before, for 2 hours after, and during bicycle exercise at a work loads of 25, 50, 75, 100, 125, 150, and 175 W. Both the N- and C-terminus of the ANF prohormone were released simultaneously with graded exercise in direct proportion to the intensity of the work load, measured objectively via maximal oxygen consumption (VO2max), respiratory quotient, and heart rate. Both the N-terminus and C-terminus of the ANF prohormone had strong positive correlations (p less than 0.001) with blood pressure, heart rate, VO2max, and respiratory quotient. Following exercise, the C-terminus returned to preexercise levels within 30 minutes, while the N-terminus remained significantly elevated at 30 and 60 minutes postexercise, reflecting the longer half-life of the N-terminus in the circulation.

Adult

Aprotinin blocks the binding of pro atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 to human placental membranes.

Two peptides with natriuretic and diuretic properties consisting of amino acids 1 to 30 and 31 to 67 of the 98 amino acid N-terminal end of the prohormone of atrial natriuretic factor, which normally circulates in humans, were investigated to determine if they have specific binding sites of placental membranes. Competitive binding experiments revealed that atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 (i.e., C-terminus) each had specific and separate binding sites. The dissociation constants for atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 binding to human placental membranes were similar at 4.3 +/- 0.6 nmol/L, 3.1 +/- 0.4 nmol/L, and 2.9 +/- 0.5 nmol/L, respectively. Each peptide bound to the placental membranes between 10(-8) and 10(-11) mol/L but could bind to the other peptides' receptors only at supraphysiologic concentrations of 10(-6) and 10(-7) mol/L. The protease inhibitor aprotinin (50 micrograms/ml) blocked the binding of the atrial natriuretic peptides 1 to 30, 31 to 67, and 99 to 126 to their respective receptors. These results suggest that atrial natriuretic peptides 1 to 30 and 31 to 67 do not work through the atrial natriuretic factor receptor but rather have their own separate and distinct receptors on placental membranes and that the protease inhibitor aprotinin antagonizes their respective binding to placental membranes, suggesting that integral membrane proteases may be modulators of atrial natriuretic peptides receptor function.

Aprotinin

The N-terminal and C-terminal portions of the atrial natriuretic factor prohormone increase during preeclampsia.

The influence of preeclampsia on the circulating concentrations of the 28-amino-acid carboxy terminus (C-terminus) (i.e., atrial natriuretic factor) and the amino terminus (N-terminus) of the 126-amino-acid atrial natriuretic factor prohormone (pro ANF) was studied in the third trimester with the use of three specific radioimmunoassays that recognize: (1) atrial natriuretic factor (i.e., amino acids 99 to 126), (2) the whole 98-amino-acid N-terminus, and (3) amino acids 31 to 67 from the midportion of the N-terminus of the prohormone. The C-terminus was significantly increased (p less than 0.001) in the third trimester in women with preeclampsia, the mean +/- SEM of 15 subjects was 150 +/- 7 pg/ml versus 89 +/- 7 pg/ml in the third trimester in 12 women during normal pregnancies and 65 +/- 2 pg/ml in 19 healthy nonpregnant women. The whole 98-amino-acid N-terminus, likewise, was significantly increased (p less than 0.001) in women with preeclampsia to 4706 +/- 629 pg/ml versus 2160 +/- 79 pg/ml in women in the third trimester of normal pregnancies and versus the circulating concentration of 1847 +/- 127 pg/ml in healthy nonpregnant women. ProANF 31 to 67 mean circulating concentration in preeclampsia was 4638 +/- 725 pg/ml, which was also significantly (p less than 0.001) increased compared with its mean circulating concentration in the third trimester of normal pregnancy of 1758 +/- 83 pg/ml or that in healthy nonpregnant women (1400 +/- 105 pg/ml). The circulating concentrations of both the N-terminus and C-terminus of the atrial natriuretic factor prohormone decreased within 24 hours after delivery in contrast to a normal pregnancy in which they both increase post partum. These results indicate a marked difference in the metabolism of both the N-terminus and the C-terminus of the atrial natriuretic factor prohormone in women with preeclampsia versus that in women with normal pregnancies or that in healthy nonpregnant women.

Adolescent

Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction.

This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.

Adult

Release of ANF, proANF 1-98, and proANF 31-67 from isolated rat atria by atrial distension.

The purpose of the present study was to determine if ANF and the NH2-terminus of the ANF prohormone are secreted simultaneously in response to atrial distension in isolated perfused rat atria. The experiments were conducted in paced left atria perfused with a modified Krebs buffer. Atrial pressure was increased from a baseline level of 2 mmHg to 8-9 mmHg for 60 minutes (distension) and then returned to 2 mmHg for 60 minutes in one group (n = 9) of isolated atria. In a second group of atria (n = 6), atrial pressure was maintained at approximately 2 mmHg throughout the experimental period. ANF secretion averaged 100 pg/min during the three 10-minute periods immediately preceding the increased atrial pressure and increased to 600-800 pg/min (P less than 0.001) when atrial pressure was raised. Secretion of the proANF 31-67 peptide increased from a value of approximately 100 pg/min immediately prior to distension to a peak of over 200 pg/min during distension (P less than 0.01). Secretion of proANF 1-98 increased from an average of 1.25 ng/min during the three periods immediately prior to distension to a peak of 2.5 ng/min during distension (P less than 0.01). These data indicate that ANF and the NH2-terminus of the ANF prohormone appear to be simultaneously secreted by isolated paced atria.

Animals

Increased release of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone during immersion-induced central hypervolemia in cirrhotic humans.

The role of peptides from the N-terminus and C-terminus of the 126 amino acid (a.a.) atrial natriuretic factors (ANF) prohormone in modulating renal sodium and water handling in cirrhotic patients has not been defined. Eight cirrhotic individuals were evaluated; their mean basal circulating concentration of the C-terminus (a.a. 99-126; i.e., ANF) was 25 +/- 2 fmol/ml, not different from the 22 +/- 1 fmol/ml value found in 54 normal volunteers. On the other hand, the basal circulating concentrations of the whole N-terminus (a.a. 1-98) and the midportion of the N-terminus (namely a.a. 31-67; pro ANF 31-67) of the ANF prohormone in these cirrhotic subjects of 704 +/- 52 and 654 +/- 83 fmol/ml were significantly elevated (p less than 0.05; ANOVA) in comparison to control values (531 +/- 25, 317 +/- 22 fmol/ml, respectively). Following equilibration on a 10 mmol/day sodium diet, the responsiveness of the N-terminus and C-terminus of ANF prohormone to 3 h of water immersion, which induces marked acute central volume expansion, was evaluated in these 8 seated cirrhotic patients. There was a prompt increase in the circulating concentrations of immunoreactive (ir) pro ANF 1-98 (whole N-terminus), ir pro ANF 31-67, and ir ANF (C-terminus) within 15 min of immersion (p less than 0.05; ANOVA) compared to their preimmersion values. The response of circulating ir pro ANF 1-98, pro ANF 31-67, and ANF concentrations in these 8 cirrhotic subjects to immersion was significantly greater (p less than 0.05; ANOVA) than that of 7 healthy volunteers undergoing an identical 3-hour immersion study. With cessation of immersion, the C-terminus decreased within 30 min to a concentration not significantly different from preimmersion values, whereas the N-terminus and pro ANF 31-67 remained significantly elevated after 1 h.

Adult

Change in plasma immunoreactive N-terminus, C-terminus, and 4,000-dalton midportion of atrial natriuretic factor prohormone with hemodialysis.

Plasma concentrations of the immunoreactive N-terminus, C-terminus and 4,000-dalton midportion of the N-terminus of the atrial natriuretic factor (ANF) prohormone were measured before and after hemodialysis in 13 patients with end-stage renal disease. There was a significant (p less than 0.001) fall in the mean plasma concentration of the C-terminus (i.e. ANF, amino acids 99-126 of the prohormone) from 123 +/- 25 to 80 +/- 22 fmol/ml (mean +/- SEM) with dialysis. The whole N-terminus, on the other hand, increased from 9,336 +/- 2,011 to 11,021 +/- 2,134 fmol/ml after dialysis (p less than 0.002). Pro ANF 31-67 (i.e. amino acids 31-67 of the prohormone) increased postdialysis from 27,775 +/- 4,300 to 31,040 +/- 4,840 fmol/ml (p less than 0.003). Only 1.5% of pro ANF 1-98 and pro ANF 31-67 were cleared by the dialyzer membrane while 15% of ANF crossed the membrane. Thus, with hemodialysis the C-terminus decreases while the N-terminus and pro ANF 31-67 from the midportion of the N-terminus of the ANF prohormone increase in plasma which is partially explained by their respective abilities to cross the dialyzer membrane.

Aged

Food intake and body positional change alter the circadian rhythm of atrial natriuretic peptides excretion into human urine.

The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor prohormone contains two natriuretic and vasodilatory peptides consisting of a.a. 1-30 (proANF 1-30) and a.a. 31-67 (proANF 31-67). The N-terminus and C-terminus (a.a. 99-126, i.e., ANF--also a vasodilatory peptide) circulate normally in humans with a circadian peak at 04:00 h in plasma. To determine if the N-terminus and C-terminus of the ANF prohormone are present in urine and possibly have a circadian variation in urine, six healthy volunteers had urine samples hourly while awake and every 3 h during sleep for five consecutive days obtained for radioimmunoassay. The sleep-awake pattern was varied so that after 2 days of normal sleep (supine)-awake (upright) positions, these volunteers were supine from 15:00 h on the third day until 10:00 h of the fourth day. They were then upright until 19:00 h that day when they became supine again until 02:30 h, and then were upright until 10:00 h of day 5. Three radioimmunoassays that immunologically recognize (a) the whole N-terminus (i.e., amino acids 1-98), (b) the midportion of the N-terminus (amino acids 31-67), and (c) the C-terminus of the ANF prohormone were utilized. ProANF 1-98, proANF 31-67, and the ANF radioimmunoassays each detected their respective peptides in urine. A circadian peak for each of these peptides was detected at 04:00 to 05:00 h whether the person was supine or upright during the night, which were significantly (p less than 0.001) higher than their concentrations in the afternoon of the previous days. Assuming a supine position during the day caused a significant (p less than 0.01) two- to threefold increase in these peptides in the urine. Food intake also increased the concentrations of proANF 1-98, proANF 31-67, and ANF in urine (p less than 0.001). Fluid intake when abstaining from food throughout the day lowered the concentration of these peptides in the urine. It was concluded that there is a circadian rhythm in both the N-terminus and C-terminus of the ANF prohormone excretion into urine with a peak at 04:00 h irrespective of posture, but that both posture and food and fluid intake throughout the day significantly influence the excretion of these peptides into the urine, with supine posture and food increasing their concentrations in the urine while fluid intake decreases their concentrations in the urine.

Adult

Atrial natriuretic factor: a possible new gastrointestinal regulatory peptide.

Although associated primarily with the cardiovascular system, atrial natriuretic factor (ANF) has been found to increase the magnitude of duodenal contractions and may play a role in salt and water absorption across gastrointestinal epithelium. Because secretory diarrhea and increased peristalsis are commonly associated with conditions related to hypergastrinemia, we examined an animal model of hypergastrinemia (fundusectomy) to evaluate a possible role for ANF. Sprague-Dawley rats underwent either fundusectomy or sham operation. Circulating levels of gastrin (1085 +/- 105 vs 59 +/- 5 pg/ml), ANF (209 +/- 50 vs 59 +/- 10 pg/ml), and pro-ANF 1-98 (786 +/- 80 vs 599 +/- 49 pg/ml) were elevated significantly 3 months after fundusectomy versus control animals. The increased levels of ANF and pro-ANF 1-98 correlated with the increased gastrin levels (p less than 0.05). Tissue content of ANF and pro-ANF 1-98 were determined at sequential sites in the stomach and small intestine. In normal rats ANF concentrations were greatest in the small intestine; pro-ANF 1-98 content was similar in all tissues except ileum (increased). In rats that underwent fundusectomy, ANF and pro-ANF 1-98 were markedly increased in duodenum compared with all other tissues. Only duodenum showed a difference in peptide levels between normal rats and rats that underwent fundusectomy, (ANF, 1.5 +/- 0.5 vs 16.7 +/- 2.3 ng/gm; pro-ANF 1-98, 0.6 +/- 0.3 vs 51.2 +/- 36.1 ng/gm). Circulating ANF and pro-ANF 1-98 are increased in rats that have undergone fundusectomy. Our results suggest that duodenum may be the source of these increased levels.

Animals

The N-terminus, C-terminus, and vessel dilator of the ANF prohormone are present in the urine and increase with ventricular fibrillation.

The N-terminus consisting of amino acids (a.a.) 1-98 (i.e., proANF 1-98), C-terminus (i.e., ANF; a.a. 99-126) and midportion of N-terminus consisting of a.a. 31-67 (proANF 31-67; Vessel Dilator) of the 126 a.a. ANF prohormone were present in the urine in 5-to-8-fold increased concentrations versus their plasma concentrations in 6 dogs under basal conditions. With acute coronary occlusion the right atrial plasma concentrations of these peptides increased two-to-three-fold, while in the urine only proANF 31-67 increased (3.5-fold). Ventricular fibrillation caused a 4-to-10-fold increased secretion into the right atrial chamber with a simultaneous 3-to-4.7-fold increase in the urine of proANF 1-98, proANF 31-67, and ANF. This investigation demonstrates that proANF 1-98, proANF 31-67 and ANF are normally present in urine and increase in the urine with cardiac stimuli that cause their release from the heart.

Animals