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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 7 (1980), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In Sprague-Dawley rats, two-kidney, one-clip renal hypertension was induced, and the drinking behaviour as well as total fluid and sodium intake were studied before and for 16 days after the operation.2. When water alone was offered as drinking fluid, the blood pressure reached values that were by about 20 mmHg higher than those in the rats which had free choice of drinking water or 2% saline.3. In those rats which had water and 2% saline to drink, the total sodium and fluid intake rose transiently for three days, as compared with that of the sham-operated controls, and increased steeply starting from the 7th and 10th day, respectively. When a tighter stenosis of the renal artery was induced, the pressure rose more rapidly, and the total fluid and sodium intake increased continuously after the operation until the end of the experiment.4. A positive correlation was demonstrable between the height of blood pressure and the total daily intake of fluid and sodium, respectively.5. The relation between the total daily fluid and the total daily sodium intake followed a straight regression line.6. The hypertensive rats which had a high total sodium intake responded to the withdrawal of the 2% saline solution, within 2 days, with increased water intake, decreased food intake, and loss of body weight, whereas the blood pressure remained high.7. In the two-kidney, one-clip hypertension, no ‘critical level of blood pressure’ can be defined, beyond which the contralateral kidney starts to lose sodium.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 56 (1978), S. 23-29 
    ISSN: 1432-1440
    Keywords: Renale Hypertonie ; Entfernung einer Nierenarterienstenose ; Renaler Salz- und Flüssigkeitsverlust ; Renin-Angiotensin System ; Renal hypertension ; Removal of one artery stenosis ; Salt and fluid loss ; Renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effect of removal of one renal artery stenosis on renal sodium and fluid excretion and on the activity of the renin-angiotensin system (RAS) has been investigated in three types of renal hypertension of rats. Blood pressure fell in all experimental models after declamping, independently of changes in urinary sodium and water excretion or plasma angiotensin II (ANG II). Plasma concentrations of ANG II did not rise in response to salt and fluid loss induced by declamping when the contralateral kidney had been removed or when it was depleted from renin. A high renin content of the declamped kidney prevented major salt and fluid loss, whereas renin depletion of this kidney was accompanied by an exaggerated natriuresis and diuresis. Besides this tubular modulation of renal salt and water handling by the local RAS, glomerular filtration rate could be reduced by a stimulated activity of this system in plasma, indicated by a close relationship between serum urea and plasma ANG II levels.
    Notes: Zusammenfassung An drei verschiedenen Modellen des renalen Hochdrucks der Ratte wurde der Einfluß der Entfernung einer Nierenarterienstenose auf die renale Salz- und Wasserausscheidung, die Aktivität des Renin-Angiotensin Systems und die Höhe des Blutdrucks untersucht. Der erhöhte Blutdruck fiel nach Entklammerung in allen Modellen auf Normalwerte ab, unabhängig von den ausgeschiedenen Mengen an Salz und Flüssigkeit und den Änderungen der Plasma Angiotensin II Konzentrationen. Dabei wurden stimulierte Werte für Angiotensin II im Plasma als Folge des Salz- und Flüssigkeitsverlustes nach Entklammerung nur dann beobachtet, wenn die kontralaterale Niere nicht zuvor bereits entfernt oder reninverarmt war. Der plötzliche Anstieg des renalen Perfusionsdruckes nach Entfernung der Stenose führte zu starken Salz- und Flüssigkeitsverlusten, wenn der Reningehalt der betreffenden Niere gering war, während ein hoher Nierenreningehalt mit einer verringerten Elektrolyt- und Wasserausscheidung einherging. Neben dieser tubulären Modulation der renalen Salz- und Wasserausscheidung durch das lokale Nierenrenin-Angiotensin System kann die Stimulation dieses Systems im Plasma über Veränderungen der glomerulären Filtrationsrate die Nierenfunktion beeinflussen. Dies wird deutlich in Situationen, die mit renalem Salz- und Wasserverlust einhergehen; dabei finden sich enge Beziehungen zwischen der Höhe der Plasma-Harnstoff- und der Angiotensin II Werte.
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  • 3
    ISSN: 1432-1440
    Keywords: Angiotensin II ; Diabetes insipidus Ratten ; Antidiurese ; SQ 14 225 ; Furosemid ; Angiotensin II ; Diabetes insipidus rats ; Antidiuresis ; SQ 14225 ; Furosemide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2×2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2×2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.
    Notes: Zusammenfassung Bei Brattleboro-Ratten mit hereditärem hypothalamischen Diabetes insipidus (DI Ratten) wurden folgende Fragen untersucht: a) Wirken exogenes and endogenes Angiotensin II (AII) antidiuretisch bei Diabetes insipidus? b) Vermittelt AII den antidiuretischen Effekt von Furosemid? Ergebnisse: 1. AII (5 mg/kg s.c. in Ö1) und Furosemid (50 mg/kg i.p.) verminderten die Urin- und erhöhten die renale Natriumausscheidung. Furosemid führte zu einem zweifachen Anstieg der AII Plasma Konzentration und zur Verminderung der Plasma-Natrium Konzentration. 2. SQ 14 225 (2×2,5 mg/kg p.o.), ein Hemmer des Angiotensin I Converting Enzym, führte zu einer Zunahme der Urin- und der renalen Natriumausscheidung. 3. Auch wenn die Bildung von AII mit SQ 14 225 (2×2,5 mg/kg p.o.) blockiert wurde, reduzierte Furosemid die Urinausscheidung, obwohl die AII Plasma Konzentration 2,5fach vermindert war. Wir schließen daraus, daß Plasma AII bei DI Ratten antidiuretisch wirken kann. Allerdings vermittelt AII nicht den antidiuretischen Effekt von Furosemid.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 56 (1978), S. 87-90 
    ISSN: 1432-1440
    Keywords: β-Rezeptorenblocker ; peripherer Widerstand ; β 1-Selektivität ; β-adrenergic blocking agents ; Peripheral resistance ; β 1-selectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effects of the beta-adrenergic blocking agents propranolol, pindolol, atenolol, bunitrolol, and methypranol on the vascular resistance of isolated perfused hindlimbs of rats were investigated. At concentrations of 0.01 µg/ml in the perfusate dl-propranolol und pindolol significantly increased vascular resistance by blockade ofβ 2-receptor mediated vasodilatation, whereas atenolol, bunitrolol and methypranol had no effect on peripheral resistance at this concentration. With increasing concentrations up to 10 µg/ml all drugs, with the exception of atenolol, caused vasodilatation. We conclude that the specificity of beta-blocking agents can be established in the isolated perfused hindlimb vasculature of rats through its effect on vascular resistance. The lack of inhibition of vascularβ 2-receptors at low concentrations of atenolol and also bunitrolol and methypranol show relative selectivity forβ 1-receptors. The differential effects ofβ-adrenergic agents on vascular resistance may have significance for the clinical use of the drugs.
    Notes: Zusammenfassung Untersucht wurde der Einfluß derβ-Rezeptorenblocker Propranolol, Pindolol, Atenolol, Bunitrolol und Methypranol auf den Gefäßwiderstand der isoliert perfundierten Hinterextremität der Ratte. Bei einer Konzentration von 0,01 µg/ml im Perfusat erhöhten dl-Propranolol und Pindolol den Widerstand deutlich, da die durchβ 2-Rezeptoren vermittelte Vasodilatation ausgeschaltet wurde. Atenolol, Bunitrolol und Methypranol hatten dagegen bei dieser Konzentration keinen Einfluß auf den peripheren Widerstand. Mit steigenden Konzentrationen bis zu 10 µg/ml wirkten alle Pharmaka mit Ausnahme von Atenolol vasodilatatorisch. Wir folgern, daß die Selektivität derβ-Rezeptorenblocker in der isoliert perfundierten Hinterextremität der Ratte durch ihren Effekt auf den Gefäßwiderstand festgestellt werden kann. Wie Atenolol zeigen auch Bunitrolol und Methypranol relative Selektivität fürβ 1-Rezeptoren, da sie in niedrigen Konzentrationen die vaskulärenβ 2-Rezeptoren nicht beeinflussen. Der unterschiedliche Einfluß derβ-Rezeptorenblocker auf den Gefäßwiderstand könnte für die klinische Anwendung der Medikamente Bedeutung haben.
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  • 5
    ISSN: 1432-1440
    Keywords: Hyponatremia ; Vasopressin ; Thirst ; Diuretics ; Cardiac failure ; Cirrhosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Because hyponatremia is frequently associated with preceding diuretic treatment and unrestricted fluid indake — conditions which have not been addressed sufficiently in published literature — we studied the pathophysiology and the clinical setting of such hyponatremia in a large group of internal medicine patients. We observed: a) Of an initial 310 patients with chemical hyponatremia only 204 (64%) had an associated plasma hypoosmolality. Sience a normal plasma osmolality excludes a disturbance of water metabolism only the 204 patients with hypoosmolar hyponatremia were included in the study. This data shows that plasma osmolality is an essential measurement in any evaluation of hyponatremia. b) In 204 consecutive patients with hypoosmolar hyponatremia the electrolyte disturbance was related to advanced congestive cardiac failure in 25%, decompensated liver cirrhosis in 18%, volume contraction in 28%, syndrome of inappropriate antidiuretic hormone secretion in 19% and renal insufficiency in 4%. c) Plasma vasopressin was measurable in 90% of the 204 patients. It is known that radioimmunoassays to measure vasopressin fail to reliably detect low concentrations of circulating vasopressin (〈0.5 pg/ml). It may therefore be stated that hypoosmolar hyponatremia was generally characterized by a failure of antidiuretic hormone suppression. d) Mean daily fluid intake of hyponatremic patients was 2.35±0.15 l. In the presence of stimulated vasiopressin this large a fluid intake is bound to worsen the severity of hyponatremia. e) Of 204 patients 126 were treated with diuretics at the time of study. In these patients hyponatremia worsened during such treatments and was associated with evidence of prerenal azotemia. However there were no significant differences between diuretic-treated and -untreated patients with respect to plasma vasopressin stimulation and amount of fluid intake. In conclusion, stimulated vasopressin and high fluid intake explain the hyponatremia observed in the present study. This applied similary to diuretictreated and -untreated patients.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 56 (1978), S. 131-138 
    ISSN: 1432-1440
    Keywords: Sympathische Aktivität ; Plasma Noradrenalin ; Adrenalin ; Dopamin ; Gefäßreaktivität ; Uptake Aktivität ; Genetische Hypertonie ; Sympathetic activity ; Plasma noradrenaline ; Adrenaline ; Dopamine ; Vascular reactivity ; Uptake activity ; Spontaneous hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Differences in sympathetic vascular tone between Wistar Kyoto rats (WKR) and stroke prone spontaneously hypertensive rats (spSHR) were determined by comparing the following parameters: sympathetic activity was evaluated by determinations of plasma catecholamines (noradrenaline, adrenaline, dopamine) combined with the measurement of the neuronal and extraneuronal uptake of noradrenaline using an isolated rat heart preparation. The responsiveness of vascular smooth muscle to vasopressor agents was tested in the isolated perfused hindlimb preparation. At the age of 5, 12, 15, and 28 weeks sympathetic nervous activity was significantly higher in spSHR than in WKR since plasma noradrenaline was elevated by almost 50% in the presence of an unaltered activity of the uptake mechanisms. The responsiveness of vascular smooth muscle to noradrenaline was markedly enhanced in spSHR. Besides increased maximal vasoconstriction in response to BaCl2 (20 mmol/l) after potassium chloride depolarization or supramaximal doses of noradrenaline (10−3 mol/l), a supersensitivity of vascular smooth muscle to noradrenaline could also be detected in spSHR (age 5 weeks). The threshold dose and the ED50 were reduced by 25% in spSHR in response to noradrenaline infusions. No changes in threshold or ED50 were found in response to potassium chloride depolarization. The stimulated sympathetic activity in spSHR and the increased responsiveness of resistance vessels to noradrenaline, both contribute to the rise in sympathetic vascular tone. The finding of an increased sympathetic vascular tone in very early stages of hypertension suggest that this factor, producing a primary increase in total peripheral resistance underlies the development of high blood pressure in spSHR.
    Notes: Zusammenfassung Unterschiede des sympathischen Gefäßtonus zwischen spontan hypertonen Ratten (spSHR) und Wistar Kyoto Ratten (WKR) wurden an Hand folgender Größen erfaßt: Die sympathische Aktivität wurde ermittelt durch die Bestimmung der Plasmakatecholamine (Noradrenalin, Adrenalin und Dopamin) bei gleichzeitiger Messung der neuronalen und extraneuronalen Wiederaufnahme von Noradrenalin im isolierten Präparat (Langendorff Herz). Die Ansprechbarkeit glatter Gefäßmuskulatur auf vasopressorische Substanzen wurde in der isoliert perfundierten Hinterextremität der Ratte gemessen. Die sympathische Aktivität war bei spSHR im Alter von 5, 12, 15 und 28 Wochen gesteigert, da die Konzentration von Noradrenalin im Plasma um 50% bei unveränderter neuronaler und extraneuronaler Wiederaufnahme erhöht war. Die Ansprechbarkeit der glatten Gefäßmuskulatur gegenüber Noradrenalin war bei spSHR verstärkt. Neben einer stärkeren maximalen Vasokonstriktion nach supramaximalen Dosen von Noradrenalin (10−3 mol/l) oder BaCl2 (20 mmol/l) fand sich eine spezifische Überempfindlichkeit der einzelnen glatten Muskelzelle gegenüber Noradrenalin bei 5 Wochen alten spontan hypertonen Ratten. Während nach Kaliumdepolarisation keine Unterschiede in der Schwellendosis oder der ED50 auftraten, waren diese bei spSHR für die Noradrenalin-induzierten Widerstandserhöhungen um 25% vermindert. Die stimulierte sympathische Aktivität sowie die erhöhte Ansprechbarkeit der Widerstandsgefäße gegenüber Noradrenalin bei spSHR sind Ursache des gesteigerten sympathischen Gefäßtonus, der über eine Erhöhung des peripheren Widerstandes die Entwicklung des hohen Blutdrucks bei der genetischen Hypertonie der Ratte verursacht.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 68 (1997), S. 654-661 
    ISSN: 1433-0385
    Keywords: Key words: Assessment of risk ; Esophagectomy ; Risk score systems. ; Schlüsselwörter: Risikoerfassung ; Oesophagektomie ; Risiko-Score-System.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Ziel der präoperativen Risikoabschätzung ist die Senkung der postoperativen Morbidität und Letalität durch eine Identifizierung gestörter Organfunktionen welche durch gezielte Maßnahmen bereits präoperativ oder durch eine problemorientierte postoperative Therapie verbessert werden können. Die präoperative Risikoerfassung nimmt damit Einfluß auf die Operationsindikation, den Operationszeitpunkt, die Verfahrenswahl und das postoperative Management. Eine notwendige Voraussetzung dafür ist es, relevante Organfunktionen mit möglichem Einfluß auf den postoperativen Verlauf zu erfassen und diese im Hinblick auf den geplanten Eingriff zu bewerten. Dieses Vorgehen gewinnt vor allem bei den heute immer umfangreicheren elektiven chirurgischen Eingriffen zunehmend an Bedeutung. In der Notfallsituation müssen dagegen die gegebenen Rahmenbedingungen in der Regel akzeptiert werden, so daß hier der präoperativen Risikoabklärung eine untergeordnete Rolle zukommt. Die objektive Risikoabschätzung erfolgt durch die Erfassung mit Bewertung von Lebensalter, Allgemein- und Ernährungszustand, pulmonale, kardiovasculäre, hepatische und Nierenfunktion, sowie Kooperationsfähigkeit des Patienten. Je nach Art und Umfang des geplanten Eingriffs kommt den einzelnen Organfunktionen eine unterschiedliche Bedeutung zu. Auf dem Boden von Basisuntersuchungen und erweiterter Diagnostik wird eine präoperative Risikoabschätzung möglich. Allgemeingültige und aus mehreren Faktoren zusammengesetzten Klassifikationssysteme zur Identifizierung von Risikogruppen haben sich mit Ausnahme einzelner und auf bestimmte Eingriffe zugeschnittene Risiko-Scores, in der klinischen Anwendung bisher jedoch nicht breit durchgesetzt. Am Modell der Oesophagektomie beim Patienten mit Oesophaguscarinom konnten wir jedoch modellhaft zeigen, daß eine quantitative Aussage über das peri- und postoperative Risiko des Patienten anhand physiologischer und präoperativ verfügbarer Parameter möglich ist und sich durch den konsequenten Einsatz eines validierten Risiko-Score-Systems die postoperative Letalität deutlich senken läßt. Die Entwicklung und Validierung ähnlicher Score-Systeme für andere Eingriffe erscheint damit wünschenswert.
    Notes: Summary. The aim of preoperative risk analysis is to reduce postoperative morbidity and mortality by identification of compromised organ function which can be improved by targeted preoperative measures and problem-oriented postoperative therapy. Ideally, therefore, preoperative risk assessment, influences the timing of the surgical procedure, the choice of the surgical approach, and the postoperative management. Identification of preexisting relevant disorders that may influence the postoperative course is an essential prerequisite of risk analysis. While preoperative risk analysis today gains in importance with the increasing extent of elective surgical procedures, preoperative risk evaluation still plays a minor role in the emergency situation when the given patient-dependent risk usually has to be accepted. Objective risk evaluation depends on the general and nutritional status, the pulmonary, cardio-vascular, hepatic, and renal function, and the cooperation of the patient. These factors, however, clearly have to be seen in relation to the type and extent of the planned surgical procedure. The selection of additional tests of organ function, exceeding the standard tests required prior to any surgical intervention, must be guided by the extent of the planned surgical procedure, the physiologic alterations associated with the surgical procedure, and the suspected underlying organ dysfunction. Generally accepted multifactorial classification systems to identify patients at risk for a wide spectrum of surgical procedures are currently not available. Using the model of esophagectomy in patients with esophageal cancer we could, however, demonstrate that a quantitative assessment of the peri- and postoperative risk based on preoperatively available physiologic parameters is possible and markedly reduces postoperative mortality when applied prospectively. The development and validation of similar risk-score systems for other surgical procedures should be considered.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Anaesthesist 48 (1999), S. 718-726 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Instabile Angina pectoris, Therapie ; Glykoprotein (GP) IIb/IIIa Rezeptorantagonisten ; Azetylsalizylsäure ; Haparin, niedermolekulares ; PTCA ; Stentimplantation, instabile Angina pectoris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zum Thema Pathogenetisch liegt der instabilen Angina pectoris meist eine Ruptur der fibrösen Kappe einer lipidreichen Plaque zugrunde. Dies führt zur Aktivierung, Adhäsion und Aggregation von Thrombozyten, also zu Thrombose und Gefäßverschluß. Weitgehend belastungsunabhängig treten Ischämiesymptome auf und werden im Gegensatz zur stabilen Angina pectoris, deren Ischämiesymptome belastungsabhängig sind, als instabile Angina pectoris bezeichnet. Die vorliegende Übersicht zeigt den derzeitigen Stand der Behandlungskonzepte für die instabile Angina pectoris auf, die ebenso wie beim Myokardinfarkt in Richtung interventioneller Maßnahmen gehen, medikamentös kombiniert mit Azetylsalizylsäure, niedermolekularem Haprin und Glykoprotein (GP) IIb/IIIa Rezeptorantagonisten. Dabei wird die PTCA immer häufiger durch Stentimplantation ergänzt. Die Dynamik dieser Entwicklung läßt sich allein daraus ablesen, daß die erste koronare Stentimplantation gerade erst ein gutes Dezennium (1987) zurückliegt. Ob sich eine so aktiv vorgehende Therapiestrategie “flächendeckend” in Deutschland durchführen läßt, stimmt nachdenklich und muß aus Organistations- und Kostengründen dahingestellt bleiben. Wünschenswert wäre das im Hinblick auf die wesentliche Risikoverbesserung akuter Konorarsyndrome natürlich. Organisatorisch ist neben qualitätssichernden Maßnahmen auch eine vertretbare Entfernung zur nächstgelegenen Herzchirurgie erforderlich, falls weiterführende operative Maßnahmen geboten sind.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 395 (1982), S. 71-74 
    ISSN: 1432-2013
    Keywords: Noradrenaline ; Adrenaline ; Vascular reactivity ; Noradrenaline uptake ; Phosphate depletion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma catecholamines and vascular response to noradrenaline were studied in phosphate depleted rats. Phosphate depletion was induced in rats by dietary phosphorus deprivation for 6 weeks. Basal plasma concentrations of noradrenaline, adrenaline and dopamine were elevated in phosphate depleted rats compared to pairfed control rats. After exposure to cold (4° C, 45 min) the rise in plasma catecholamines was much more pronounced in phosphate depleted rats. In the isolated perfused rat heart, the uptake of tritiated noradrenaline was unchanged. In the isolated perfused hindlimb preparation the vascular response to noradrenaline, but not to potassium chloride and argininevasopressin was significantly diminished in phosphate depleted rats. It is concluded that in phosphate depletion sympathetic activity is elevated and vascular response to noradrenaline diminished.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 89 (1994), S. 524-534 
    ISSN: 1435-1803
    Keywords: Anoxia ; cyanide ; exocytosis ; nonexocytotic release ; neuropeptide Y
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nicotine-induced noradrenaline was investigated in perfused guinea pig hearts subjected to metabolic blockade that was caused either by anoxia or by cyanide intoxication. Noradrenaline, neuropeptide Y, and dihydroxyphenylethyleneglycol (DOPEG) were determined in the coronary venous overflow. Neuropeptide Y is a sympathetic cotransmitter of nordrenaline, and concomitant release of both transmitters indicates an exocytotic, calcium-dependent release mechanism, whereas neuropeptide Y overflow does not occur during nonexocytotic noradrenaline release. Nonexocytotic, calcium-independent noradrenaline release, however, is associated with an increase of DOPEG overflow, which is the main intraneuronal metabolite of noradrenaline formed by monoamine oxidase if oxygen is present. Anoxia per se caused a nonexocytotic release of noradrenaline starting after 10 min of anoxia and reaching peak levels at 30 min. During anoxia, nicotine (3 and 10 μmol/l) accelerated and enhanced noradrenaline overflow, i.e., the period between the onset of anoxia and the begin of noradrenaline release was shortened and peak levels were increased. Nicotine-induced noradrenaline release was accompanied by neuropeptide Y overflow. The action of nicotine was further evaluated during energy depletion caused by cyanide. As anoxia did, cyanide administration alone resulted in noradrenaline release. In accordance with a nonexocytotic mechanism and due to the presence of oxygen, this release of noradrenaline was accompanied by an increase of DOPEG. When added 10 min after the onset of energy depletion, nicotine (10 μmol/l) caused a brief but marked enhancement of exocytotic noradrenaline release, since this release was calcium-dependent and was accompanied by a significnat rise of neuropeptide Y overflow. In absence of extracellular calcium to avoid exocytosis, concomitant administration of nicotine (3–100 μmol/l) and cyanide caused a concentration- dependent acceleration of both the overflow of noradrenaline and DOPEG, whereas overflow of neuropeptide Y was not increased, thus indicating a nonexocytotic release mechanism. In conclusion, the application of nicotine during myocardial energy depletion increases overflow of noradrenaline by both calcium-dependent exocytotic release and calcium-independent nonexocytotic release mechanisms.
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