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  • 1
    ISSN: 1432-1440
    Keywords: Key words Guanylyl cyclase ; Atrial natriuretic peptide ; Induction ; Lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  There have been conflicting reports about the occurrence and/or activity of atrial natriuretic peptide (ANP) sensitive guanylyl cyclase in the immune system. This study reports on ANP-sensitive guanylyl cyclase mRNA expression and guanylyl cyclase activity in human peripheral blood mononuclear cells (PBMC). Reverse transcription polymerase chain reaction (RT-PCR) shows that activated human PBMC of healthy blood donors express functional active ANP-sensitive guanylyl cyclase after vitro culture, whereas freshly isolated PBMC show neither specific mRNA for particulate guanylyl cyclase nor ANP-sensitive activity of this enzyme. To define the subpopulation of PBMC expressing this enzyme, cultivated PBMC were subfractioned and analyzed by RT-PCR and in situ PCR. Only CD3+ PBMC showed mRNA for ANP-sensitive guanylyl cyclase. Induction of the guanylyl cyclase required coincubation with other cells, indicating that a factor or factors secreted from cells other than CD3+ cells induces this expression. In summary, ANP-sensitive guanylyl cyclase is an inducible enzyme in human CD3+ PBMC in contrast to other cells where it is considered to be constitutive.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Calcium channel blockers ; exercise test ; atrial natriuretic peptides ; urodilatin ; hemodynamics ; natriuresis ; diuresis ; BAY t 7207
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8±2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0±1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8±4.1 mmHg) than after placebo (95.7±3.5 mmHg; p+0.024), and HR was higher after BAY (76.8±3.5 bpm) than after placebo (69.5±3.6 bpm; p+0.049). Plasma ANF tended to be higher after BAY (31.2±5.6 pg/ml) than after placebo (26.7±5.0 pg/ml), and plasma cGMP was not different (BAY 3.4±0.3, placebo 3.8±0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130±28% after placebo but only by 36±11% after BAY (p+0.011). In parallel, plasma cyclic GMP increased by 61±13% after placebo and by 20±8% after BAY (p+0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r+0.717; p+0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46±0.11 to 0.90±0.22% (p+0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Keywords Metalloproteinases ; Antagonists and inhibitors ; Neutral endopeptidase 24.11; natriuretic peptides ; atrial ; congestive heart failure ; haemodynamics ; cyclic GMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Inhibition of neutral endopeptidase 24.11 (NEP) prevents degradation of plasma atrial natriuretic peptide (ANP), a substance with vasodilatory and natriuretic properties. The aim of the study was to investigate the haemodynamic and endocrine effects of the NEP inhibitor candoxatril in patients with congestive heart failure (CHF). Methods: In a randomized double-blind, parallel group study design, 24 patients with CHF received a 10-day oral drug treatment with candoxatril (25, 100 or 400 mg b.i.d.) or placebo. Invasive haemodynamics and laboratory parameters were measured on days 1 and 10. Results: On the first treatment day, candoxatril produced a dose-dependent increase in plasma cyclic GMP, the second messenger of ANP. At doses of 100 and 400 mg, candoxatril induced an increase (!) in systemic vascular resistance (SVR) and a decrease in cardiac index (CI), which was not observed with placebo and the lower candoxatril dose. Conclusions: Despite significant activation of the ANP system, reflected by a dose-dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril induced systemic vasoconstrictory rather than vasocilatory effects in patients with CHF. Therefore NEP inhibition by candoxatril may not exhibit beneficial haemodynamic effects in CHF.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1285
    Keywords: Schlüsselwörter Paroxysmale supraventrikuläre Tachykardie – Urodilatin – ANP – zyklisches Guanosinmonophosphat ; Key words Paroxysmal supraventricular tachycardia – urodilatin – ANP – cyclic GMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Patients with paroxysmal supraventricular tachycardia (SVT) may have a polyuria after termination of tachycardia. There is increasing evidence that the renal peptide urodilatin (ANP(95–126)) – and not plasma ANP (ANP(99–126)) – is the member of the natriuretic peptide family mediating natriuresis and diuresis in man. In patients with SVT we, therefore, analyzed the relationship between diuresis, natriuresis, plasma ANP, urinary urodilation excretion and renal excretion of cyclic GMP, the second messenger in the ANP system. During and after clinical presentation with spontaneously occurring SVT, two patients with AV-nodal and one patient with atrioventricular reentry tachycardia (heart rate 160 to 200 bpm) were studied. Urinary urodilatin excretion was correlated to diuresis (r = 0.73) and natriuresis (r = 0.93); similarily urinary cyclic GMP excretion was related to diuresis (r = 0.80) or natriuresis (r = 0.87; p 〈 0.001, respectively). In contrst, there was no significant correlation between plasma ANP concentration and diuresis (r = 0.28, n.s.) or natriuresis (r = 0.11, n.s.). As an explorative analysis, stepwise multiple linear regression identified urinary urodilatin as the most important contributor to diuresis and natriuresis after SVT. These data on polyuria after spontaneous SVT further support the view that in man urodilatin is the member of the natriuretic peptide family participating in kidney physiology.
    Notes: Zusammenfassung Patienten mit paroxysmaler supraventrikulärer Tachykardie (SVT) haben oftmals eine Polyurie nach Terminierung der Tachykardie. Jüngere Untersuchungen weisen darauf hin, daß beim Menschen das renale Peptid Urodilatin (ANP(95–126)) – und nicht Plasma-ANP (ANP(99–126)) – der an Natriurese und Diurese beteiligten Mediator aus der Familie natriuretischer Peptide ist. Im Rahmen einer Untersuchung bei Patienten mit SVT wurde deshalb die Beziehung zwischen Diurese, Natriures, ANP-Plasma-Spiegeln, renaler Ausscheidung von Urodilatin und cGMP, dem second messenger im ANP-System, analysiert. Während und nach klinischer Präsentation mit einer spontan auftretenden SVT wurden zwei Patienten mit AV-Knoten-Tachykardien und ein Patient mit artioventrikulärer Reentry-Tachykardie (Frequenz 160 bis 200/min) untersucht. Die renale Urodilatin-Sekretion war mit der Diurese (r = 0,73) und Natriurese (r = 0,93) korreliert; eine ähnliche Beziehung bestand zwischen renaler cGMP-Ausscheidung und Diurese (r = 0,80) sowie Natriurese (r = 0,87; jeweils p 〈 0,001). Im Gegensatz hierzu ergab sich keine signifikante Korrelation zwischen ANP-Plasmaspiegeln und Diurese (r = 0,28, n.s.) oder Natriurese (r = 0,11, n.s.). Im Rahmen einer explorativen Analyse konnte mittels schrittweiser logistischer Regression die renale Urodilation-Sekretion als wichtigster unabhängiger Faktor für die Diurese und Natriurese nach SVT identifiziert werden. Diese Daten zur Polyurie nach spontanter SVT stimmen mit jüngsten Ergebnissen zur Physiologie der Nierenfunktion überein, die zeigen, daß Urodilatin das an der Regulation der Nierenfunktion beteiligte natriuretische Peptid ist.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Der Internist 38 (1997), S. 427-437 
    ISSN: 1432-1289
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zum Thema Eines der wichtigen zellulären Übertragungssysteme ist zyklisches Guanosinmonophosphat (cGMP). Zusammen mit Stickstoffmonoxid (NO), das aus dem Endothel freigesetzt wird und hormonelle und mechanische Signale überträgt, bildet es das NO/cGMP-System. In dieser Arbeit wird zunächst über die biochemischen und pharmakologischen Grundlagen dieses Systems referiert. Einen besonders breiten Raum nimmt sodann die Darstellung des klinischen Potentials ein. Durch die Relaxation der glatten Muskulatur ergeben sich in den meisten Organsystemen und bei sehr unterschiedlichen Krankheitsbildern durch Vasodilatation therapeutische Optionen, nicht minder durch die Beeinflussung nitrerger Nerven, der Zellproliferation und durch weitere Eigenschaften. Während die induzierte und erhöhte NO-Synthese nach jetzigem Kenntnisstand im Gefäßsystem im wesentlichen als therapeutisch vielversprechend gilt, mit Ausnahme allerdings im Schock, ist die erhöhte NO-Synthese im Rahmen chronisch entzündlicher Prozesse weniger erwünscht. Die Zukunft wird erweisen, wie sich unter solchen Umständen eine Therapie gegen NO auswirkt.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of medical systems 19 (1995), S. 69-76 
    ISSN: 1573-689X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Migration from space medicine toward telemedicine services is described by potential application areas in highly populated and remote areas of Europe. Special emphasis is laid upon links between mobile patient monitoring and health care in remote areas. Pilot projects are described for home (mobile) monitoring of newborn infants endangered by sudden infant death (SID) and adults suffering from sleep apnoea. Health care in remote areas is described by the “TeleClinic-project” which will link national nodes for telemedicine services in several European states for the mobile European citizen. Another project describes the future potential of robotics for semiautonomous ultrasound diagnostics and for realtime interaction of remote experts with diagnostics and therapy.
    Type of Medium: Electronic Resource
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