Biomedical subjects

D L Vesely

Publications and source records attributed to D L Vesely.

At least 55 records · Page 3Linked to original sources

PubMed1996

Atrial natriuretic peptide increases adrenomedullin in the circulation of healthy humans.

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolated from extracts of human pheochromocytoma. ADM's biologic properties are nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic properties. The present investigation was designed to determine if one or more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body weight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P < 0.001) increase in the circulating concentration of adrenomedullin secondary to the ANF infusion but no increase in adrenomedullin with the long acting natriuretic peptide, vessel dilator, or kaliuretic peptide infusions. The four-fold increase of adrenomedullin in the circulation persisted throughout the infusion of ANF, but returned to pre-infusion levels within 30 minutes of stopping the ANF infusion. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resulted in a 2 1/2-fold increase (P < 0.05) in the circulating concentration of adrenomedullin. There was a significant (P < 0.01) diuresis and blood pressure lowering effect with each of the atrial natriuretic peptides in the present investigation. This investigation suggests that 1) atrial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attributed to atrial natriuretic factor may be partially due to adrenomedullin since both increased during the ANF infusion and both have similar biologic effects. As opposed to atrial natriuretic factor, adrenomedullin was not increased by long acting natriuretic peptide, vessel dilator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.

Adrenomedullin↗

PubMed1996

Processing of kaliuretic peptide in human plasma and serum.

High performance-gel permeation chromotography (HP-GPC) evaluation of human plasma and serum incubated at 37 degrees C for 0, 0.5, 1, 1.5, 2, 4, 8, and 24 h after the addition of the human synthetic form of kaliuretic peptide revealed only a peak where the pure synthetic form of kaliuretic peptide elutes and that this peak decreased by 60% or greater in plasma-EDTA, plasma-heparin, and serum within 30 min. The metabolic processing of kaliuretic peptide in plasma-EDTA, plasma-heparin, and serum, respectively, was complete in 2 h with only 4%, 1%, and 2% of kaliuretic peptide's originally added concentration being still present.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

Atrial natriuretic peptides negatively and positively modulate circulating endothelin in humans.

The present investigation was designed to examine the effect of four atrial peptide hormones with vasodilatory properties on the circulating immunoreactive (ir) levels of the vasoconstrictive peptide endothelin (ET) in 36 healthy human subjects. Circulating levels of human ET and cyclic guanosine monophosphate ([cGMP], a potential mediator of the effects of atrial peptides), were measured every 30 minutes during 1-hour preinfusion, 1-hour infusion, and 3-hour postinfusion periods. Atrial natriuretic factor ([ANF] amino acid (aa) 99 to 126 of the 126-aa ANF prohormone) and kaliuretic peptide (aa 79 to 98 of this same prohormone) significantly (P<.05) decreased circulating ET concentrations. Kaliuretic peptide effects were early and ANF effects were delayed until kaliuretic peptide effects began to wane. Long-acting natriuretic peptide (LANP), consisting of aa 1 to 30 of the ANF prohormone, on the other hand, significantly (P<.05) increased ET circulating concentrations during a 1-hour infusion period. The increase in ET in the circulation secondary to LANP became nonsignificant, although it was still elevated, within 30 minutes of ceasing LANP infusion. Vessel dilator, consisting of aa 31 to 67 of the ANF prohormone, and infusion of vehicle alone did not significantly change circulating levels of ET during the 5 hours of this investigation. ANF infusion increased plasma cGMP sevenfold, but plasma cGMP had decreased to only onefold above normal during the period that ANF had an effect on circulating ET levels. There was not any significant increase or decrease in plasma cGMP concentrations secondary to the other atrial peptide hormones. These data suggest that kaliuretic peptide and ANF negatively modulate circulating ET concentrations, while LANP, which is released simultaneously with ANF in response to physiologic stimuli, positively modulates circulating ET concentrations to help maintain circulating ET within a narrow normal range. The data from the present investigation would further suggest that circulating cGMP levels do not mediate the various atrial peptide effects on circulating ET levels.

Adult↗

PubMed1996

Processing of long-acting natriuretic peptide and vessel dilator in human plasma and serum.

High performance-gel permeation chromatography (HP-GPC) evaluation of human plasma and serum incubated at 37 degrees C up to 24 h after the addition of long-acting natriuretic peptide (LANP) revealed a 25% decrease in LANP's peak at 2 h followed by an increase in plasma without EDTA at 8 h (p < 0.001). Vessel dilator's HP-GPC peak did not decrease until after 8 h of incubation. These findings help explain the prolonged half-lives and 6-24 higher plasma concentrations of vessel dilator and LANP compared to atrial natriuretic factor and kaliuretic peptide, which are completely degraded in plasma within 2 h.

Atrial Natriuretic Factor↗

PubMed1996

Increased release of kaliuretic peptide during immersion-induced central hypervolemia in cirrhotic humans.

Kaliuretic peptide is a recently discovered potent stimulator of potassium and water excretion. Its role in modulating renal water handling in cirrhotic patients has not been defined. The responses of circulating kaliuretic peptide and atrial natriuretic factor in 8 cirrhotic subjects to water immersion were significantly greater (p < 0.05) than those of 7 healthy volunteers. With cessation of immersion, atrial natriuretic factor decreased within 30 min to preimmersion values, whereas kaliuretic peptide remained significantly elevated > 1 h, suggesting a slower clearance for kaliuretic peptide. The peak diuretic response to immersion corresponded in a temporal fashion to the peak circulating concentration of kaliuretic peptide, suggesting a possible physiological role of kaliuretic peptide in modulating volume homeostasis in cirrhotic humans.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

Congestive heart failure: increased cardiac and extracardiac atrial natriuretic peptide gene expression.

OBJECTIVES: The present investigation was designed to determine if atrial natriuretic peptide (ANP) gene expression increases in extracardiac as well as within the heart in congestive heart failure. METHODS: Congestive heart failure (CHF) was induced by producing cardiac hypertrophy secondary to an aortocaval fistula in Sprague-Dawley rats. To characterize this model, control and CHF rats had cardiac catheterizations and transthoracic echocardiography. ANP messenger RNA was measured by RNAase protection analysis in atria, ventricles, liver, colon, and stomach of CHF and sham rats and quantitated by 2-D scanning. The product of ANP gene expression was determined in each of these tissues with high performance-gel permeation chromatography. To help determine if increased degradation of atrial natriuretic peptides occur in congestive heart failure, the circulating concentrations and the excretion of the atrial natriuretic peptides into urine were measured by specific radioimmunoassays. RESULTS: ANP steady-state mRNA increased 4.2 +/- 0.05 and 4.3 +/- 0.06-fold, respectively, in the antrum of the stomach and within the heart ventricle of CHF rats compared with age-matched sham rats. ANP gene expression was present but not increased in atria, liver, and gastrointestinal tract of the CHF rats. High-performance gel permeation chromatography revealed that the product of this ANP gene expression within the stomach and heart ventricle in CHF animals was the ANP prohormone. There was not any decrease in the metabolism of these peptides by the kidney in CHF. CONCLUSIONS: ANP steady-state mRNA increases in extracardiac (i.e., stomach antrum) tissue as well as in the ventricle of the heart in CHF. The product of the ANP gene expression, i.e., the ANP prohormone is the same in the extracardiac tissues as within the heart. Whether the increased extracardiac ANP steady-state mRNA and its resultant increased atrial natriuretic peptides helps prevent bowel wall edema in CHF needs to be elucidated.

Animals↗

PubMed1995

Vessel dilator is associated with survival after acute myocardial infarction.

To assess whether infarct size, ischemic area and/or survival correlates with circulating atrial natriuretic peptides (long acting sodium stimulator, vessel dilator, or atrial natriuretic factor), these peptides were measured in a canine model of acute myocardial infarction. Elevations in the circulating concentrations of atrial natriuretic factor, vessel dilator, and long acting sodium stimulator were significant (P < 0.05) within 6 min of coronary occlusion of the left anterior descending coronary artery. The percentage of ischemic myocardium ranged from 20 to 67% with a mean of 37 +/- 17%. The area of infarction ranged from 1 to 13% with the infarcted area of non-survivors being twice that of survivors. Both the ischemic and infarcted areas correlated (P < 0.05) with the circulating concentrations of these atrial natriuretic peptides. Survival correlated also with the circulating plasma concentrations of vessel dilator, atrial natriuretic factor and long acting sodium stimulator (P < 0.05). When these circulating concentrations were evaluated, however, by determining their area under their respective concentrations curves and expressing each as the log area under plasma concentration-time curve (area under the curve) per kg of weight (Y = 58.48X-23.62; r = 0.825; P = 0.0009), vessel dilator was the only atrial natriuretic peptide that correlated with survival.

Animals↗

PubMed1995

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.

Animals↗

PubMed1995

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 AM 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.

Adult↗

PubMed1995

Cirrhosis with ascites: increased atrial natriuretic peptide messenger RNA expression in rat ventricle.

BACKGROUND/AIMS: Atrial natriuretic peptides (ANPs) are increased in the circulation of cirrhotics with ascites; however, it is unknown whether this increase is caused by increased synthesis or a decrease in the metabolic processing of these peptides. ANP gene expression in the liver, atria, ventricles, and gastrointestinal tract of cirrhotic vs. control rats was studied as was their metabolism. METHODS: Sprague-Dawley rats developed cirrhosis with ascites approximately 20 weeks after weekly intragastric instillation of carbon tetrachloride. Their circulating, ascitic, and urinary levels of ANPs were measured by radioimmunoassays. ANP gene expression was measured by a ribonuclease protection assay. RESULTS: ANP gene expression was increased 2.8- to 4.1-fold in the ventricles of cirrhotic rats compared with age-matched healthy rats. ANP gene expression was present but not increased in the liver, atria, and gastrointestinal tract of cirrhotic rats. No increase of metabolic processing of these peptides was found in the circulation. Cardiac ultrasonography and catheterization revealed no ventricular dilation or increased ventricular pressure. CONCLUSIONS: Elevation of circulating ANPs with cirrhosis was associated with increased ventricular steady-state ANP messenger RNA concentrations. The increased ANP gene expression in cirrhosis seems to involve a novel mechanism not related to stretch because neither increased ventricular pressure nor dilation was present.

Analysis of Variance↗

PubMed1995

Dimethyl sulfoxide inhibits renal Na(+)-K(+)-ATPase at a site different from ouabain and atrial peptides.

The present investigation was designed to determine 1) if dimethyl sulfoxide (DMSO) inhibits renal cortical and medullary Na(+)-K(+)-ATPase at the ouabain binding site and 2) if this inhibition of Na(+)-K(+)-ATPase by. DMSO involves atrial natriuretic peptides or prostaglandins. DMSO (10%) inhibited renal cortical and medullary Na(+)-K(+)-ATPase 31% and 29.5%, respectively. Ouabain (0.5 mM) inhibited renal cortical and medullary Na(+)-K(+)-ATPase 32% and 35%, respectively. When DMSO and ouabain were added together the inhibition of renal cortical and medullary Na(+)-K(+)-ATPase was 55% and 59%, respectively. Atrial natriuretic peptides consisting of amino acids 1-30 (i.e., long acting natriuretic peptide), 31-67 (vessel dilator), 79-98 (kaliuretic peptide) and 99-126 (atrial natriuretic factor, ANF) of the 126 amino acid ANF prohormone inhibited renal cortical Na(+)-K(+)-ATPase 27.5%, 20%, 37.5% and 0% at a 10(-11)M concentration. The addition of DMSO caused a doubling (P < 0.05) of this inhibition. Likewise, these same atrial peptides inhibited renal medullary Na(+)-K(+)-ATPase 27.8%, 19.2%, 39.5%, and 0% with DMSO doubling (P < 0.05) their Na(+)-K(+)-ATPase inhibition. There was not any additive effect of any of the atrial peptides with ouabain. Naproxen, a prostaglandin inhibitor, completely blocked atrial peptides and ouabain's inhibition of Na(+)-K(+)-ATPase but not DMSO's. Each of the atrial peptides except ANF increased prostaglandin E2 synthesis while DMSO did not increase prostaglandin E2 synthesis. This investigation suggests that DMSO has its inhibiting effect at a site different from the ouabain binding site on renal Na(+)-K(+)-ATPase since it has an additive effect with ouabain in inhibiting Na(+)-K(+)-ATPase while the atrial peptides appear to have their effect at the ouabain binding site. As opposed to the atrial peptides, DMSO's mechanism of inhibiting Na(+)-K(+)-ATPase does not appear to involve prostaglandin E2.

Animals↗

PubMed1995

Case report: hypoglycemia secondary to a meningioma.

Hypoglycemia secondary to a meningioma that has not metastasized to the liver has not been reported previously. A 41-year-old woman with a spinal cord meningioma first diagnosed 5 years previously with 3 recurrences in the spinal cord resulting in 4 neurosurgical procedures was admitted with a serum glucose of 23 mg/dL. Six months before the current admission, the patient was noted to have an abdominal mass of 10 cm not present on previous computed tomography. Three months later, the mass was 15.2 cm, and on the current admission, had increased to 23 cm and encased both the aorta and inferior vena cava. A needle biopsy of this mass before referral to the authors' hospital with hypoglycemia revealed that it was a meningioma. Evaluation of the etiology of the hypoglycemia, which required continuous intravenous glucose therapy, revealed that circulating insulin, C-peptide (i.e., connecting peptide), insulin-like growth factor-I (i.e., somatomedin-C) and insulin-like growth factor-II were all normal or low. Serum cortisol also was not low. Based on her endocrine evaluation, the hypoglycemia was secondary to the large mass of tumor cells, requiring a large glucose uptake to sustain its growth. After radiation therapy of 3,770 CGy to the meningioma, the patient became euglycemic without glucose supplementation.

Adult↗

PubMed1995

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.

Adult↗

PubMed1995

Atrial natriuretic hormones originating from the N-terminus of the atrial natriuretic factor prohormone.

1. Four peptide hormones consisting of amino acids 1-30 (Long Acting Sodium Stimulator), 31-67 (Vessel Dilator), 79-98 (Kaliuretic Stimulator) and 99-126 (atrial Natriuretic Factor [ANF]) originate from the same 126 amino acid ANF prohormone. 2. Each of these four peptide hormones circulates as a distinct peptide with vessel dilator and long acting sodium stimulator circulating at 10- to 24-fold higher concentrations than ANF while kaliuretic stimulator circulates at a three-fold higher concentration than ANF. 3. Each of these peptide hormones is released with an increase in central volume causing stretch of the atrium of the heart and with rapid heart beats greater than 125 beats/min. 4. Each of these peptide hormones lowers blood pressure, causes a diuresis and enhances sodium and/or potassium excretion. 5. In disease states which retain sodium and water such as congestive heart failure (CHF), each of these atrial peptides increases in the circulation proportionately to the severity of sodium retention, but of the radioimmunoassays to each of these hormones only the vessel dilator radioimmunoassay differentiates between mild (class I) CHF and healthy individuals.

Atrial Natriuretic Factor↗

PubMed1995

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.

Animals↗

PubMed1995

Kaliuretic peptide: the most potent inhibitor of Na(+)-K+ ATPase of the atrial natriuretic peptides.

The present investigation was designed to determine whether atrial natriuretic peptides consisting of amino acids 1-30 (i.e. long-acting natriuretic peptide), 31-67 (vessel dilator), 79-98 (kaliuretic peptide), and 99-126 [atrial natriuretic factor (ANF)] of the 126 amino acid ANF prohormone inhibit sodium-potassium-ATPase as part of their mechanism(s) of action for producing a natriuresis and/or kaliuresis. Kaliuretic peptide, long-acting natriuretic peptide, vessel dilator and ANF at their 10(-11) M concentrations inhibited Na(+)-K(+)-ATPase 39.5%, 27.8%, 19.2%, and 4% respectively, in bovine renal medulla, whereas their inhibition in renal cortical membranes was 37.5%, 27.5%, 20%, and 0%, respectively. Ouabain (0.5 mM) inhibited kidney medullary Na(+)-K(+)-ATPase 45% and in the cortex, 38%. There was no additive effect of any of these peptides with ouabain suggesting that they are interacting with the same site on the Na(+)-K(+)-ATPase as ouabain. To help elucidate the mechanism of these peptides' interaction with Na(+)-K(+)-ATPase, naproxen (0.5 mM), an inhibitor of prostaglandin synthesis, and direct measurement of prostaglandin E2 by RIA were used. Naproxen completely blocked the inhibition of Na(+)-K(+)-ATPase by kaliuretic peptide, long-acting natriuretic peptide, and vessel dilator suggesting that their inhibition of Na(+)-K(+)-ATPase in both the kidney medulla and cortex are mediated by prostaglandins. Direct measurement of prostaglandin E2 revealed that kaliuretic peptide > long-acting natriuretic peptide > vessel dilator increased prostaglandin E2 synthesis, whereas ANF did not have any effect. Of interest, angiotensin II and ouabain inhibition of Na(+)-K(+)-ATPase were also completely blocked by naproxen.

Analysis of Variance↗