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  • 1
    Electronic Resource
    Electronic Resource
    Cardenolide analogs. 14. Synthesis and biological activity of glucosides of 17.beta.-modified derivatives of digitoxigenin (1982)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 25 (1982), S. 1222-1226 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00352a025
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  • 2
    Electronic Resource
    Electronic Resource
    DISEASE-INDUCED CHANGES IN α-ADRENOCEPTOR-MEDIATED CARDIAC AND VASCULAR RESPONSES IN RATS (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 21 (1994), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The physiological relevance of cardiac and vascular α-adrenoceptors may increase in disease states in which β-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR).2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR.3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats.4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats.5. Thus, disease states which alter β-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the α1-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via α-adrenoceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1994.tb02575.x
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  • 3
    Electronic Resource
    Electronic Resource
    ION CHANNEL MODULATORS AS POTENTIAL POSITIVE INOTROPIC COMPOUNDS FOR TREATMENT OF HEART FAILURE (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 21 (1994), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Current positive inotropy therapy of heart failure is associated with major problems: digoxin and the phosphodiesterase inhibitors can cause life-threatening toxicity while β-adrenoceptor agonists become less effective inotropic compounds as heart failure progresses. A new approach to positive inotropy is ion channel modulation.2. An increased influx of Na+ during the cardiac action potential, as measured with DPI 201–106 and BDF 9148 which increase the probability of the open state of the Na+ channel, will increase force of contraction.3. Activation of L-type Ca2+ channels with Bay K 8644 will increase influx of Ca2+ and increase the force of contraction. However the Ca2+ channel activators developed to date have little potential for the treatment of heart failure as they are vasoconstrictors.4. Blocking cardiac K+ channels is a possible mechanism of positive inotropy. Terikalant inhibits the inward rectifying K+ channel, tedisamil inhibits the transient outward K+ channel and dofetilide is one of the newly developed inhibitors of the slow delayed outward rectifying K+ channel. All these drugs prolong the cardiac action potential to increase Ca2+ entry and force of contraction.5. Thus drugs which increase Na+ influx or block K+ channels represent exciting possibilities for positive inotropy and the potential of these compounds for the treatment of heart failure needs to be fully evaluated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1994.tb02454.x
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  • 4
    Electronic Resource
    Electronic Resource
    COMPARISON OF INOTROPIC AND CHRONOTROPIC RESPONSES IN RAT ISOLATED ATRIA AND VENTRICLES (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 18 (1991), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The positive inotropic and chronotropic responses to adrenoceptor agonists (noradrenaline, phenylephrine), to compounds which increase cAMP by post-adrenoceptor mechanisms (forskolin, theophylline and dibutyryl cAMP) and to calcium chloride were measured in isolated rat atria and papillary muscles from both ventricles.2. Noradrenaline produced similar maximal inotropic responses to calcium chloride in all tissues. Forskolin gave similar responses to calcium chloride in atrial but not ventricular tissues; the reverse was observed with dibutyryl cAMP. Phenylephrine and theophylline produced significantly smaller inotropic responses than calcium chloride in all tissues, especially in ventricular tissues.3. Maximal chronotropic responses to noradrenaline, theophylline and dibutyryl cAMP were similar. Forskolin produced significantly greater responses while calcium chloride and phenylephrine produced significantly smaller responses than noradrenaline.4. These results show that the maximal positive inotropic response of some agonists is markedly dependent on the tissue chosen. Further, chronotropic responses in right atria do not mimic inotropic responses in left atria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1991.tb01393.x
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  • 5
    Electronic Resource
    Electronic Resource
    Pirfenidone attenuates ischaemia–reperfusion injury in the rat small intestine (2002)
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 29 (2002), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Pirfenidone, an antifibrotic compound with anti-inflammatory effects, has been investigated in a rat model of acute experimental ischaemia–reperfusion injury of the small intestine.2. Occlusion of the superior mesenteric artery in young adult female rats for 30 min followed by reperfusion for 120 min induced significant local and systemic effects, including tissue haemorrhage with oedema, elevated serum concentrations of tumour necrosis factor (TNF)-α, neutropenia, hypotension and bradycardia.3. Administration of pirfenidone (200 mg/kg, p.o., i.v. or i.p.) 30 min before occlusion completely inhibited the increase in serum TNF-α concentrations. Pirfenidone inhibited, but did not completely prevent, tissue damage in the small intestine, as well as hypotension and oedema, but neutropenia and bradycardia were not significantly changed by treatment.4. Thus, pirfenidone effectively moderates both local and some systemic effects of ischaemia–reperfusion injury in the rat small intestine model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1440-1681.2002.03766.x
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  • 6
    Electronic Resource
    Electronic Resource
    Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: NEW DRUGS IN THE TREATMENT OF HEART FAILURE (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 22 (1995), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Current therapy of heart failure relies on diuretics, positive inotropic compounds and vasodilators. The short-term haemo-dynamic benefits, especially of the cAMP generators, may be compromised by long-term limitations leading to an increased mortality. In contrast, some vasodilators, especially angiotensin converting enzyme inhibitors, improve survival even in severe heart failure.2. Modulation of Na+- or K+-channels and calcium sensitization are positive inotropic mechanisms whose promise in treatment of heart failure needs to be fully explored.3. The introduction of vasodilator therapy has been a significant advance. Newer compounds act to inhibit the endogenous vasoconstrictors angiotensin II and endothelin, or to potentiate the endogenous vasodilators atrial natriuretic factor and nitric oxide. The full potential of these compounds is yet to be realised.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1995.tb01944.x
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  • 7
    Electronic Resource
    Electronic Resource
    α1-ADRENOCEPTORS ON RABBIT AORTIC SMOOTH MUSCLE CELLS IN CULTURE AND IN EXPERIMENTAL INTIMAL THICKENING (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 22 (1995), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. This study has defined α1-adrenoceptors and their reactivity in rabbit aorta, following removal of the endothelium and formation of a myointimal thickening, and also in smooth muscle cells (SMC) in cell culture which had undergone serial passaging and changes in phenotype.2. [3H]-prazosin binding to SMC from control aorta, vessels 2 weeks after endothelial denudation and sub-cultured SMC (passage 3–6) was specific (displaceable with 10 μmol/L phentolamine), and of high affinity to a single class of sites (Kd range: 71–114 pmol/L). The maximum binding density (Bmax) of α1-adrenoceptors on SMC from the neointima (11105 ± 771 sites/cell) was not significantly different to that of control medial SMC (14014 ± 2472 sites/cell). However, SMC cultured to passage 6, showed a 2-fold increase in Bmax (30227 ± 4349 sites/cell).3. The production of inositol phosphates (IP1, IP2 and IP3) by SMC following 10μmol/L phenylephrine was assayed. Both freshly-dispersed aortic SMC and sub-cultured SMC were stimulated to produce increased inositol phosphates by the addition of phenylephrine which was completely inhibited by pre-incubation with 10 μmol/L phentolamine, suggesting that the stimulation was via α1-adrenoceptors.4. Maximal contractile responses of isolated thoracic and abdominal aortic rings to KCl (100 mmol/L), 5-HT and phenylephrine were unchanged two weeks after endothelial denudation. However, phenylephrine was significantly less potent (2.7-fold) in both areas of the aorta, while the potency of 5-HT was significantly enhanced (2.7-fold) after endothelial denudation only in the abdominal aorta.5. The decreased sensitivity of the rabbit aorta to α1-adrenoceptor agonists following endothelial denudation and the formation of a myointimal thickening is not due to changes in affinity or density of α1-adrenoceptors. However multiple passaging of SMC in culture leads to an increase in α1-adrenoceptor density. This change can be related to the altered cytodifferentiation of irreversible synthetic state SMC which are similar to those in atherosclerotic lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1995.tb02326.x
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  • 8
    Electronic Resource
    Electronic Resource
    POSITIVE INOTROPIC AND VASOCONSTRICTOR RESPONSES TO 14β-AMINOPREGNANE DERIVATIVES IN ISOLATED TISSUES FROM THE GUINEA-PIG (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 17 (1990), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The objective of this study was to compare the positive inotropic and vasoconstrictor responses in guinea-pig isolated tissues of the aminosteroid derivatives LND 623 and LND 796 and the cardiac glycoside ouabain.2. Ouabain (- log EC50, 6.66±0.04, n= 11) was more potent as a positive inotropic agent on guinea-pig right ventricular papillary muscles than either LND 623 (- log EC50, 6.26±0.08, n= 6) or LND 796 (- log EC50 5.66±0.05, n= 7). All compounds gave similar maximal increases in force of contraction. However, the ratio of the maximally effective concentration to the concentration giving 25% of the maximal response was approximately doubled for the aminosteroids compared with ouabain.3. Ouabain (- log EC50 6.27), LND 623 (- log EC50 6.24) and LND 796 (- log EC50 5.43) produced slowly developing contractions of guinea-pig thoracic aortic rings.4. These results indicate that, while the aminopregnane derivatives and ouabain produce qualitatively similar results, the therapeutic range for the positive inotropic responses is greater for the aminosteroids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1990.tb01359.x
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  • 9
    Electronic Resource
    Electronic Resource
    ANGIOTENSIN RECEPTORS IN CARDIOVASCULAR DISEASES (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 21 (1994), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix.2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases.3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density.4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density.5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists.6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients.7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype-selective agonists and antagonists to treat particular forms of cardiovascular diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1994.tb02450.x
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  • 10
    Electronic Resource
    Electronic Resource
    POSITIVE INOTROPIC RESPONSES OF THE SODIUM CHANNEL MODULATOR BDF 9148 IN DISEASED RAT MYOCARDIUM (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 22 (1995), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. This study has defined the positive inotropic responses to the sodium channel modulator BDF 9148 in rats with hypertension, thyroid dysfunction, diabetes or dwarfism. Concentration-response curves to BDF 9148 and calcium chloride were determined in isolated left atria and left ventricular papillary muscles.2. BDF 9148 increased force of contraction in left ventricular papillary muscles in all disease states with maximal responses comparable to calcium chloride. BDF 9148 potency was significantly decreased in muscles from diabetic rats only.3. BDF 9148 produced similar responses in left atria except from hyperthyroid rats where negative inotropic responses only were measured. This exception confirms that the left atria is an imperfect model for ventricular responsiveness.4. Thus, the increase in force of contraction in the ventricles as a consequence of sodium channel modulation by BDF 9148 is maintained in these disease states unlike responses to α-or β-adrenoceptor agonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1995.tb02033.x
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