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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 18 (1991), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Basal and stimulated guanylate cyclase activity during ADP-induced human platelet aggregation in comparison with the actions of sodium nitroprusside (SNP) on platelets was investigated.2. Sodium nitroprusside exhibited both ex vivo and in vitro antiplatelet effects, as assessed by inhibition of subsequent ADP-induced aggregation in platelet-rich plasma. A strong correlation between decrease in aggregation and increase in platelet guanylate cyclase activity in the presence of SNP was obtained.3. When SNP was administered after the induction of aggregation, it caused acceleration of disaggregation (in reversible aggregation) and produced disaggregation (under conditions of otherwise irreversible aggregation) which was time-dependent.4. Platelet aggregation was accompanied by a transient increase in platelet cyclic GMP content and guanylate cyclase activation by the nitric oxide (NO) donor SNP. Changes in guanylate cyclase activity were haem-associated and probably reflected saturation of enzyme by haem.5. Maximal SNP disaggregating effect coincided with peak guanylate cyclase responsiveness to SNP.6. The present investigation provides evidence that increased responsiveness of platelet guanylate cyclase to NO during aggregation facilitates disaggregation in the presence of SNP. Thus, availability of NO (endogenous or exogenous) at sites of incipient platelet aggregation in vivo may play a pivotal role regarding limitation of this process.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In 24 patients who were undergoing coronary arteriography for the assessment of ischaemic heart disease, the relationship between the systemic and coronary vascular responses to acute intravenous digoxin administration (500 μg) and concurrent drug therapy with the calcium antagonist verapamil (group I) or a β-adrenoceptor antagonist (group II) or neither of these agents (group III) was examined.2. Systemic vascular resistance (SVR) tended to rise rapidly after digoxin injection in patients in groups II and III, and tended to decline initially in patients in group I; however, these differences were not statistically significant (variance ratio [VR] = 0.77).3. No significant differences were observed in coronary vascular responses to acute digoxin administration between the three groups of patients (VR = 0.34).4. For the entire group of 24 patients, no statistically significant digoxin-induced effects on resistance could be demonstrated in either the systemic or coronary circulations, although in individual patients vasoconstrictor effects were observed.5. We conclude that acute intravenous administration of digoxin does not consistently cause systemic or coronary vasoconstriction in patients with ischaemic heart disease. Variability in vasomotor responses to digoxin is not clearly related to concurrent drug therapy with verapamil or a β-adrenoceptor antagonist. The observation that systemic vascular resistance tends to increase in the first few minutes after digoxin injection should be addressed in future studies.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg; P〈0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg; P〈0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm5; P〈0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m2 (P〈0.05). There was a non-significant fall in heart rate.2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters.3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 22 (1995), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Recent clinical studies have raised the possibility that intermittent nitrate dose regimens, while limiting the extent of nitrate tolerance development, may trigger rebound aggravation of ischaemia after abrupt withdrawal of nitrate. To date, only limited studies have been performed to examine the mechanism of this phenomenon.2. In a bovine isolated coronary artery model, we tested the hypothesis that induction of glyceryl trinitrate (GTN) tolerance might affect large coronary artery responsiveness to a variety of non-catecholamine constrictor agents. Glyceryl trinitrate tolerance was induced by pre-exposure to GTN (10 μmol/L) for 60 min followed by 15 min washout. In some experiments, the effect of prior endothelial removal on putative interactions was also examined.3. Our results showed that GTN tolerance did not affect responses to KCI, the thromboxane A2 mimetic U46619, endo-thelin-1 and 5-HT, irrespective of presence or absence of endothelium. None of the constrictor agents tested induced endothelium-dependent constriction.4. We conclude that in this model of GTN tolerance induction, there is no evidence of ‘rebound’ vasoconstriction to this group of non-catecholamine vasoconstrictors with GTN withdrawal.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 24 (1968), S. 1126-1127 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Blutplasma des Menschen verengt isolierte, durchströmte kleine Blutgefässe. Dieser Effekt kommt nicht durch bekannte, gefässaktive Substanzen, sondern wahrscheinlich durch ein Protein zustande. Eine ähnliche Wirkung wurde in 2 Cohn-Fraktionen von Plasma-Proteinen gefunden, welche sich im Hundeversuch gefässdrucksenkend auswirkten. Plasma-Albumin ist an sich nicht gefässaktiv, es verstärkt aber die Wirkung der andern Substanzen.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 26 (1970), S. 790-791 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Menschenplasma enthält ein Eiweiss, welches sämtliche Blutgefässe in vitro einengt, jedoch in vivo Arterienerweiterung zu veranlassen scheint. Das Plasmaniveau von Frauen ist höher als das von Männern. Während der Schwangerschaft fällt es ab und kehrt postpartum zu dem Ausgangspunkt der Kontrollen zurück, oder es steigt sogar über diesen Ausgangspunkt hinaus.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 263 (1969), S. 332-339 
    ISSN: 1432-1912
    Keywords: Veins ; Plasma Kinins ; Venen ; Plasmakinin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused central vein of the rabbit ear constricts in response to approximately 0.5 ng of BK or kallidin injected into the perfusion flow of 10 ml/min. Constrictor responses are also elicited by several other substances including catecholamines and histamine but none approach the potency of the plasma kinins. This relative specificity together with the steep dose-response curve for kinins makes it an eminently suitable preparation for bioassay of these peptides. Rabbit veins from other sites do not have the same pattern of reactivity and no generalization is possible from these data to veins in vivo.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 6 (1976), S. 429-429 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 520-525 
    ISSN: 1432-1912
    Keywords: Key words Platelet aggregation ; Stable angina pectoris ; Sodium nitroprusside ; cGMP ; Guanylate cyclase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Platelet hyperactivity plays an important role in the pathogenesis of cardio-vascular diseases. In patients with stable angina pectoris, we have recently demonstrated that nitroglycerin suppressed the increased platelet aggregability. The anti-aggregating effect of NTG and other nitrovasodilators is mediated by platelet guanylate cyclase, which generates cyclic GMP (cGMP) in response to nitric oxide (NO) liberated from the nitrovasodilator molecule. In the current study we utilised a more “direct” NO donor, sodium nitroprusside (SNP), to examine reversal of ADP-induced platelet aggregation in comparison with intraplatelet cGMP elevation in platelets from normal subjects (n=22) and patients with stable angina pectoris (n=23). Concentrations of SNP associated with 50% reversal of aggregation were 2.7±0.4×10-7 mol/L with normal subjects and 4.5±0.5×10-6 mol/L with patients (P〈0.01). SNP produced a concentration-dependent elevation of intraplatelet cGMP content: with 10-4 mol/L SNP this was 17-fold for normals and 5-fold for patients (P〈0.01). An increase in cAMP content was seen only with 10-4 mol/L SNP, and was 157±11% of baseline in platelets from normal subjects and 138±14% in patients. There was a strong interrelationship between cGMP-stimulating and anti-aggregating effects of SNP. The decrease in cGMP responsiveness to SNP was not related to a dysfunction of platelet guanylate cyclase; neither basal nor SNP-stimulated activity of the enzyme varied significantly between normal subjects and patients. Lipophilic derivatives of cGMP (db-cGMP) and cAMP (db-cAMP) caused reversal of aggregation; there was a nonsignificant trend towards decreased responsiveness of platelets from patients to both db-cGMP and db-cAMP. The observed decrease in responsiveness of platelets from angina patients to anti-aggregating effects of the exogenous NO donor, SNP, can therefore be attributed to suppressed cGMP accumulation. These results imply reduced platelet sensitivity to endogenous NO (endothelium-derived relaxing factor); this might contribute to platelet hyperaggregability observed in angina pectoris.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 263 (1969), S. 324-331 
    ISSN: 1432-1912
    Keywords: Catecholamines ; Plasma Kinins ; Histamine ; Glucocorticoid Aldosterone ; Brenzcatechinamin ; Plasmakinin ; Histamin ; Glucocorticoid Aldosteron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The isolated perfused central vein of the rabbit ear has been used to investigate potentiation by adrenal steroids of the actions of bradykinin, histamine and noradrenaline. 2. Potentiation of all substances occurred when adrenal steroids in large doses were added to the perfusate but was neither large in magnitude nor constant in occurrence. Potentiation was seen with cortisol and dexamethasone and their potency was in the same relationship as their glucocorticoid activity. However aldosterone was roughly equi-potent with dexamethasone. 3. Thus the potentiation by steroids in this preparation is non-specific in that BK and histamine as well as noradrenaline responses are affected. The potency of steroids does not parallel either glucocorticoid or mineralocorticoid activity and so these results do not suggest an effect of steroids on either specific receptors or membrane electrolyte distribution.
    Type of Medium: Electronic Resource
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