Biomedical subjects

D L Vesely

Publications and source records attributed to D L Vesely.

At least 19 recordsLinked to original sources

PubMed2000

Vessel dilator, long acting natriuretic peptide, and kaliuretic peptide increase circulating prostaglandin E2.

Prostaglandin E2 (PGE2) increases in the circulation of persons with congestive heart failure (CHF), but the cause of this increase is unknown. Prostaglandins are not stored, therefore, they cannot be released in response to congestive heart failure itself but rather need to have their synthesis stimulated by a hormone or some other substance. Prostaglandin E2's biologic properties are nearly identical to four 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 peptide, ANP] of the 126 amino acid ANP prohormone. ANP previously has been found to have no effect on circulating PGE2 concentrations in persons with CHF. The present investigation was designed to determine if one or more of the other three atrial natriuretic peptides might increase PGE2 when infused at their respective 100 ng/kg body weight/minute concentrations for 60 minutes in persons with congestive heart failure. Vessel dilator increased PGE2 8-fold (P<0.001) in the first 20 minutes of its infusion with PGE2 remaining 2-3 fold increased (P<0.05) for 60 minutes after stopping its infusion. Long acting natriuretic peptide did not increase PGE2 until 40 minutes of its infusion but it caused the maximal increase (27-fold; P<0.001) of PGE2 of the three peptide hormones tested. Kaliuretic peptide's stimulated increase of PGE2 also began in a delayed fashion but its effects lasted the longest, with PGE2 being increased (P<0.05) for two hours after the cessation of kaliuretic peptide's infusion. This investigation demonstrates that 1) three endogenous peptide hormones increase PGE2 in the circulation and 2) suggests that the known increase in PGE2 in CHF may be in part secondary to these peptides.

Adult↗

PubMed2000

Metastatic prostate cancer (with prostate-specific antigen of 9996) presenting as obstructive jaundice.

A 78-year-old man admitted with clinical jaundice and pelvic pain had a total bilirubin level of 6.56 mg/dL, an alkaline phosphatase level of 855 U/L, and a prostate specific antigen (PSA) level of 9996 ng/mL. A computed tomogram demonstrated marked retroperitoneal, peripancreatic, periceliac, and periaortic lymphadenopathy. A bone scan revealed increased radiolabeled technetium uptake in the pelvis, vertebral column, parietooccipital region, ribs, and appendiceal skeleton. A biopsy of one pelvic lesion revealed metastatic prostate cancer. This man's obstructive jaundice and bone pain had a dramatic response to treatment with a gonadotropin-releasing hormone analog (leupro lide) and antiandrogen (bicalutamide). All bone pair and clinical signs of jaundice disappeared in 1 week His total bilirubin decreased to 0.84 mg/dL by 2 weeks His PSA values reflected this clinical response, decreasing to 4022 ng/mL in 1 week, 2680 ng/dL after 2 weeks and 1028 ng/mL after 1 month of the above therapy.

Aged↗

PubMed2000

Amelioration with vessel dilator of acute tubular necrosis and renal failure established for 2 days.

Seventeen Sprague-Dawley rats had ischemic nonoliguric acute renal failure (ARF) induced by vascular clamping resulting in their preischemic blood urea nitrogen (BUN) and creatinine levels of 16 +/- 1 and 0.56 +/- 0.05 mg/dl to increase to 162 +/- 4 and 8.17 +/- 0.5 mg/dl, P < 0.001, respectively, at day 4 of postischemia. Vessel dilator, a 37-amino-acid cardiac peptide hormone (0.3 microg x kg(-1) x min(-1) ip), decreased the BUN and creatinine levels to 53 +/- 17 mg/dl and 0.98 +/- 0.12 mg/dl (P < 0.001) in another seven animals where ARF had been established for 2 days. Water excretion doubled with ARF and was further augmented by vessel dilator. Transthoracic echocardiography revealed left ventricular dilation as a probable cause of the increase in vessel dilator in the circulation with ARF, and vessel dilator infusion reversed this dilation. At day 6 of ARF, mortality decreased to 14% with vessel dilator from 88% without vessel dilator. Acute tubular necrosis was <5% in the vessel dilator-treated rats compared with 25% to >75% in the placebo-treated ARF animals. We conclude that vessel dilator improves acute tubular necrosis and renal function in established ARF.

Acute Kidney Injury↗

PubMed2000

Regulation of atrial natriuretic peptide gene expression in gastric antrum by fasting.

Atrial natriuretic peptide (ANP) gene expression was localized in the rat gastric antrum using immunohistochemistry and in situ hybridization to mucosal cells in the lower portion of the antropyloric glands. Colocalization of immunoreactive ANP, long-acting natriuretic peptide, i.e., proANP-(1-30), and serotonin in these cells identified them to be enterochromaffin cells. Fasting for 72 h in 8-mo-old (adult) rats produced a significant (P < 0.05) decrease in the levels of ANP prohormone mRNA, immunoreactive proANP-(1-30) and ANP to approximately 33% of that of fed rats. Fasting in 1-mo-old rats had no effect on these parameters. Transcripts for natriuretic peptide receptor subtypes NPR-A, NPR-B, and NPR-C were found in both mucosa and muscle tissues of the antrum. ANP, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) stimulated the production of cGMP in antral mucosa in vitro with a potency of ANP > BNP >> CNP, suggesting that these receptors were functional. We conclude that fasting decreases ANP prohormone mRNA and its gene products, long-acting natriuretic peptide, and ANP in the antrum of adult rats.

Animals↗

PubMed1999

Environmental upregulation of the atrial natriuretic peptide gene in the living fossil, Limulus polyphemus.

Northern blot analysis revealed that atrial natriuretic peptide (ANP) gene expression occurs in heart, hematocytes and gills of the invertebrate Limulus polyphemus, the horseshoe crab. In low salinity and on land ANP prohormone messenger RNA in Limulus' heart was 32-fold less compared to that in a vertebrate heart (i.e., rat, Rattus norvegicus). ANP gene expression doubled (P < 0.05) in Limulus' heart and gills with change from land and low salinity to medium salinity and osmolality. ANP gene expression was 10-fold higher in Limulus' gills in seawater (i.e., high salinity). The products of this ANP gene expression (i.e., ANP, long acting natriuretic peptide, vessel dilator and kaliuretic peptide) were released and increased in the circulation, i.e., hemolymph, of Limulus proportional to the increase in salinity and osmolality (P = <0.01). These results suggest that modification of ANP gene expression enables animals to adapt to freshwater, seawater, and land.

Animals↗

PubMed1999

Comparison of vessel dilator and long-acting natriuretic peptide in the treatment of congestive heart failure.

BACKGROUND: Long-acting natriuretic peptide (LANP; proANF 1-30) and vessel dilator (proANF 31-67) enhance sodium and water excretion in healthy human beings. The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF). METHODS AND RESULTS: LANP and vessel dilator (100 ng/kg body weight/min, respectively) were given intravenously for 60 minutes to subjects with New York Heart Association class III CHF (n = 17) while their urine volume and sodium and potassium excretion were monitored. Vessel dilator increased urine flow more than 5-fold, which was still increased (P <.001) 3 hours after stopping its infusion. Vessel dilator enhanced sodium excretion 3-fold in subjects with CHF (P <.01), which was still significantly (P <.01) elevated 3 hours after infusion. The effects of LANP were diminished, with urine flow only increasing 2-fold (P <.05). The fractional excretion of sodium increased maximally 6-fold secondary to vessel dilator and 3-fold with LANP. The CHF control patients had no changes in the above parameters. Part of the diminished response to LANP was found to be caused by its rapid decrease in the circulation of individuals with CHF. CONCLUSIONS: These results indicate that vessel dilator has significant beneficial diuretic and natriuretic properties, which are not diminished, whereas the effects of LANP are diminished in human beings with CHF compared with healthy individuals.

Atrial Natriuretic Factor↗

PubMed1999

Elevated atrial natriuretic peptides and early renal failure in type 2 diabetic Goto-Kakizaki rats.

The present investigation was designed to determine if atrial natriuretic peptides (ANPs) are increased in a spontaneous model of non-obese type 2 diabetes, the Goto-Kakizaki (GK) rat. Four peptide hormones originating from the ANP prohormone were increased twofold (P < .05) to sixfold (P < .01) in the circulation of GK rats compared with nondiabetic Wistar rats from which the GK colony was originally derived. Thus, ANP, long-acting natriuretic peptide (LANP), vessel dilator, and kaliuretic peptide were (mean +/- SE) 497 +/- 78, 1,285 +/- 105, 457 +/- 45, and 385 +/- 87 pg/mL in GK rats, versus 78 +/- 23, 542 +/- 77, 137 +/- 26, and 134 +/- 33 pg/mL, respectively, in Wistar rats. In evaluating the cause of the increased ANPs, the blood volume of GK rats (16.2 +/- 0.4 mL) was significantly (P < .01) increased compared with Wistar rats (9.5 +/- 0.3 mL). The ventricles of GK rats were not dilated when examined by transthoracic echocardiography, but the venous system was markedly distended. GK rats had a 48% to 79% decrease in renal function (ie, increased serum creatinine and blood urea nitrogen [BUN]) compared with Wistar rats. These results indicate that circulating ANPs are increased in the GK spontaneously diabetic rat secondary to (1) increased blood volume, which leads to increased synthesis and release of ANPs, and (2) renal failure, which results in a delayed metabolic processing of these peptides. The early combined increases of the four atrial peptides collectively may contribute to the hyperfiltration that occurs in early diabetes mellitus.

Animals↗

PubMed1999

Atrial natriuretic-like peptide and its prohormone within metasequoia.

Metasequoia glyptostroboides was one of the dominant conifers in North America, Asia, and Europe for more than 100 million years since the late Cretaceous Albian Age, but Quaternary glaciations drove the Metasequoia population to apparent extinction. A small pocket of Metasequoia, however, was found in central China in the 1940s representing the only surviving population of this "living fossil" species. Atrial natriuretic peptide, a 28-amino-acid peptide hormone that causes sodium and water excretion in animals, has been found to be part of the first peptide hormonal system in lower plants. The existence of this hormonal system has never been examined within trees of any genus. High-performance gel permeation chromatography of the leaves and stems (i.e., branches) of Metasequoia followed by atrial natriuretic peptide radioimmunoassay revealed an ANP-like peptide and its prohormone (i.e., approximately 13,000 mol wt) were present in both leaves and stems of this conifer. The elution profile of ANP-like peptide in stems of Metasequoia had a shoulder to the left of where pure synthetic ANP elutes suggesting the possibility of a slightly larger peptide eluting within this shoulder secondary to alternate processing of the ANP-like prohormone and similar to what occurs with the kidney of animals. The elution profile of ANP-like peptide in the leaves of Metasequoia revealed two peaks; one where ANP elutes and a second peak suggesting a smaller peptide that has been metabolically processed. The presence of the ANP-like prohormone strongly suggests that ANP-like gene expression is occurring in both leaves and stems of Metasequoia since this prohormone is the gene product of this hormonal system. The presence of the ANP-like hormonal system in trees implies that this hormonal system may have been present early in land plant evolution to allow trees to reach heights of greater than 30 feet where a water flow-enhancing substance is absolutely necessary for water flow to occur to these heights.

Atrial Natriuretic Factor↗

PubMed1999

Hepatitis A-induced diabetes mellitus, acute renal failure, and liver failure.

A 38-year-old otherwise healthy man presented with hepatic failure (aspartate aminotransferase of 7212 U/L, alanine aminotransferase of 6629 U/L, total and direct bilirubin of 10.7 mg/dL) and acute renal failure (creatinine of 11.6 mg/dL and blood urea nitrogen of 42 mg/dL), which required hemodialysis when the creatinine increased to 21 mg/dL, with a blood urea nitrogen of 115 mg/dL, and the patient became oliguric. On admission, this patient also had a lipase of 1833 U/L, amylase of 211 U/L, glucose of 210 mg/dL, and reactive IgM antibody for acute hepatitis A. The hepatitis and acute renal failure resolved in 3 months, but this patient continues to have type II diabetes mellitus 7 years after the hepatitis A infection. This case illustrates that hepatitis A infection may be severe with liver failure, acute renal failure, and permanent diabetes mellitus as sequale of this infection.

Acute Kidney Injury↗

PubMed1998

Vessel dilator enhances sodium and water excretion and has beneficial hemodynamic effects in persons with congestive heart failure.

BACKGROUND: Vessel dilator, a 37-amino acid peptide hormone synthesized in the heart, enhances urine flow 4- to 12-fold and sodium excretion 3- to 6-fold in healthy humans. The present investigation was designed to determine whether vessel dilator might have similar beneficial effects in persons with congestive heart failure (CHF). METHODS AND RESULTS: Vessel dilator (100 ng/kg body weight per minute) given intravenously for 60 minutes to NYHA class III CHF subjects increased urine flow 2- to 13-fold, which was still increased (P<0.001) 3 hours after its infusion was stopped. Vessel dilator enhanced sodium excretion 3- to 4-fold in CHF subjects (P<0.01), which was still significantly (P<0.01) elevated 3 hours after infusion. Vessel dilator decreased systemic vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary wedge pressure 33%, and central venous pressure 27% while increasing cardiac output 34%, cardiac index 35%, and stroke volume index 24% without significantly affecting heart rate or pulmonary artery pressure in the CHF subjects. The control CHF patients did not have any changes in the above parameters. CONCLUSIONS: These results indicate that vessel dilator has significant beneficial diuretic, natriuretic, and hemodynamic properties in humans with congestive heart failure.

Adult↗

PubMed1998

Atrial natriuretic peptide increases urodilatin in the circulation.

BACKGROUND: Urodilatin is a 32-amino-acid (AA) peptide formed in the kidney. METHODS: High-performance gel permeation chromatography and high-pressure liquid chromatography evaluation of plasma followed by sensitive urodilatin and atrial natriuretic peptide (ANP) assays revealed that urodilatin does circulate distinctly from ANP. RESULTS: Urodilatin circulates at very low levels (i.e 9-12 pg/ml). Infusion of ANP increased the circulating concentration of urodilatin 135-fold (p < 0.001), suggesting that some of the effects of ANP may be mediated by urodilatin while long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide did not affect urodilatin in healthy humans (n = 30). Only ANP decreased the renal clearance of urodilatin (60-75%, p < 0.01). Urodilatin was metabolized into peptides smaller than 5 AAs as well as excreted intact into urine. CONCLUSION: Urodilatin circulates and is increased by ANP in humans.

Adult↗

PubMed1997

Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators.

OBJECTIVES: The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). METHODS: Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each = n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1-30, 31-67, and 79-98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. RESULTS: ProANPs 31-67, 1-30 and 79-98 had 100% (P = 0.01), 83% (P = 0.09) and 50% (P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31-67 significantly (P = 0.0001) discriminated between early CHF (5226 +/- 377 pg/ml) and healthy individuals (1595 +/- 157 pg/ml). The positive and negative predicative values of proANP 31-67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. CONCLUSIONS: ProANPs 31-67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.

Adrenomedullin↗

PubMed1997

Effects of lidocaine on atrial natriuretic peptide concentrations in plasma and urine.

The antiarrhythmic agent lidocaine reduces inward sodium current and increases outward potassium current. Described studies investigated the effect of lidocaine on circulating and urinary levels of atrial natriuretic peptides in an intact canine model. Surface electrocardiography was monitored along with right ventricular, left ventricular and aortic pressures, and cardiac output. Plasma and urine atrial natriuretic peptides were measured immediately before and five minutes after a five minute, 2 mg/min, intravenous lidocaine infusion. Long acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) were monitored by RIA. There were no measured hemodynamic or cardiomechanical changes noted after lidocaine infusion. Similarly, there was no change in plasma sodium or potassium, or urine sodium. There was, however, an increase in urine potassium levels. Additionally, plasma and urine LANP and ANF peptide levels were increased following lidocaine infusion, while plasma and urine concentrations of vessel dilator were not changed. These data suggest that lidocaine increases plasma and urine atrial natriuretic peptides by mechanisms other than cardiodepression and/or vasodilation.

Animals↗

PubMed1997

Atrial natriuretic peptides increase calcitonin gene-related peptide within human circulation.

Long-acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) (each infused at 100 ng/kg body weight [BW].min for 60 minutes) increased the circulating concentration of calcitonin gene-related peptide (CGRP) threefold to fourfold in 30 healthy humans. Within 30 minutes of stopping ANF infusion, the CGRP circulating concentration had returned to preinfusion levels, whereas its increase secondary to the other atrial peptides was still significant 2 to 3 hours after cessation of their infusions. There was a 50% decreased excretion (P < .001) of CGRP into the urine secondary to LANP and vessel dilator, which correlated with the increase of CGRP in the circulation. The ANF-induced 50% decreased CGRP excretion occurred after the circulating concentration of CGRP had returned to preinfusion levels. Kaliuretic peptide did not affect CGRP circulating concentration or excretion into urine. These data suggest that LANP and vessel dilator inhibit the metabolic breakdown of CGRP as part of their mechanism of increasing CGRP in plasma, whereas the ANF effect of increasing CGRP in plasma appears to be secondary to stimulating the release of CGRP.

Adult↗

PubMed1997

Signal transduction: activation of the guanylate cyclase-cyclic guanosine-3'-5' monophosphate system by hormones and free radicals.

Intracellular communication and transmission of messages for many hormones and free radicals occur after the hormones and free radicals bind to their receptors by enhancing the activity of guanylate cyclase, the enzyme that catalyzes the conversion of guanosine triphosphate to the intracellular messenger cyclic guanosine-3'-5' monophosphate (cyclic GMP). The guanylate cyclase-linked receptors exist intracellularly (ie, cytoplasmic) and in membrane-bound forms. Enhancement of guanylate cyclase by hormones or free radicals increases intracellular cyclic GMP, which closes cation channels in the kidney while activating cation channels in the retina and olfactory cilia, either directly or by cyclic GMP-dependent protein kinase. Cyclic GMP also has potent blood pressure lowering properties. Cyclic GMP promotes growth by increasing DNA, RNA, and protein synthesis. Overactivity of this system is observed in Traveler's diarrhea, whereas underactivity occurs in Chediak-Higashi syndrome in which lysosomal enzyme release and chemotaxis are defective and can be corrected in vitro by addition of cyclic GMP.

Animals↗

PubMed1997

Disposition of vessel dilator and long-acting natriuretic peptide in healthy humans after a one-hour infusion.

The present investigation was designed to determine half-lives, distribution phases and metabolic clearance of two new cardiac peptide hormones in humans. Long-acting natriuretic peptide (LANP) and vessel dilator were infused at 100 ng/kg of b.wt./min concentrations for 60 min with their respective concentrations measured by specific radioimmunoassays in plasma during and for 3 hr after infusion. The half-life of vessel dilator was 107 min, whereas the half-life of LANP was 28 min. The average time that the respective peptides were retained in the body (mean residence time) was 214 +/- 34 min for vessel dilator and 178 +/- 12 min for LANP, which indicates that they are widely distributed outside the initial space (i.e., circulation). The metabolic clearance normalized to 1.73 m2 body surface area was 241 ml/min for vessel dilator and 249 ml/min for LANP. The total body clearance normalized to 1.73 m2 body surface area was 130 ml/min for vessel dilator and 293 ml/min for LANP. The significantly (P < .001) longer half-lives and slower metabolic clearance of LANP and vessel dilator compared with atrial natriuretic factor (half-life, 2.5 min, metabolic clearance, 582-2,581 ml/min/1.7 m2) explain why these peptides circulate at concentrations 15- to 24-fold higher than atrial natriuretic factor in healthy humans.

Adult↗

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↗