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Article
The β2 subunit of nitric oxide-sensitive guanylyl cyclase is developmentally regulated in rat kidney
We have recently shown that nitric oxide activates the β2 subunit of soluble guanylyl cyclase. In the present study, we show developmental regulation of this subunit. Analysis of mRNA expression by RT-PCR and RN...
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Article
Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase
>Nitric oxide (NO) is an ubiquitous signaling molecule produced from L-arginine by NO synthase (NOS). In the vasculature, NO mediates parasympathetic endothelium-dependent vasodilation. NO may also mediate the...
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Article
Pharmacological aspects of calcium channel blockers
Calcium channel blockers (CCBs) inhibit voltagedependent L-type calcium channels. This leads to vascular smooth muscle relaxation and negative inotropic and chronotropic effects in the heart. The latter are co...
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Article
Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts
Disturbances in the cAMP production during β-adrenergic stimulation and alterations of Ca 2+ transport controlling proteins and their regulation in the sarcoplasmic reticulum might be involved in the pathogenesis...
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Article
Effects of saterinone and its enantiomers R(+)-saterinone and S(−)-saterinone on the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts
Stereoisomers often exhibit differences in their pharmacological activities. Therefore, the phosphodiesterase inhibitory effects of the cardiotonic agent saterinone in form of the racemate were investigated in...
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Article
Isoprenaline-induced increase in the 40/41 kDa pertussis toxin substrates and functional consequences on contractile response in rat heart
Chronic β-adrenoceptor stimulation leads to desensitization of the myocardial adenylyl cyclase signalling pathway which includes β-adrenoceptor downregulation and upregulation of Gi-protein α-subunits. However, t...
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Article
Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations
The present study was performed to compare the effects of the new positive inotropic phosphodiesterase III inhibitors pimobendan, adibendan, and saterinone on the isometric force of contraction in electrically...
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Article
Isoprenaline-induced increase in mRNA levels of inhibitory G-protein α-subunits in rat heart
Long-term β-adrenergic stimulation has been shown to desensitize the β-adrenoceptor/adenylyl cyclase signalling pathway at both the receptor and the G-protein level. To further elucidate the cellular mechanism...
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Article
Distinct down-regulation of cardiac β1- and β2-adrenoceptors in different human heart diseases
Cardiac β-adrenoceptor density and β1- and β2-subtype distribution were examined in human left ventricular myocardium from transplant donors serving as controls and from patients with mitral valve stenosis, aorti...
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Article
Introduction: Mechanisms of positive inotropic effects
This review deals with the principal mechanisms which are known to play a role in positive inotropism: 1) The myoplasmic Ca2+ concentration may be increased by increases in cyclic AMP. Beside receptor-mediated st...
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Article
Effects of adenosine analogues on contractile response and CAMP content in guinea-pig isolated ventricular myocytes
In the present study the effects of adenosine analogues were investigated on cAMP content and contractile response in guinea-pig ventricular myocytes. The adenosine analogues (−)-N6-phenylisopropyladenosine (R-PI...
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Article
Effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly selective adenosine receptor antagonist, on force of contraction in guinea-pig atrial and ventricular cardiac preparations
The effects of the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) on force of contraction were examined in isolated electrically driven auricles and papillary muscles from guinea-pigs...
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Article
Relation of positive inotropic and chronotropic effects of pimobendan, UD-CG 212 Cl, milrinone and other phosphodiesterase inhibitors to phosphodiesterase III inhibition in guinea-pig heart
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This study was performed to elucidate the relation between positive inotropy and phosphodiesterase inhibitio...
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Article
Pertussis toxin prevents adenosine receptor- and m-cholinoceptor-mediated sinus rate slowing and AV conduction block in the guinea-pig heart
The influence of pertussis toxin on the effects of adenosine, the adenosine receptor agonist (−)-N6-phenylisopropyladenosine (PIA) and the m-cholinoceptor agonist carbachol on heart rate and atrioventricular (AV)...
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Article
Mechanism of action and cardiotonic activity of a new phosphodiesterase inhibitor, the benzimidazole derivative adibendan (BM 14.478), in guinea-pig hearts
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The effects of adibendan (BM 14.478; 7,7-dimethyl-2-(4-pyridyl)-6,7-dihydro-3H,5H-pyrrolo[2,3-fl benzimidazol...
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Article
Evidence against a role of a pertussis toxin-sensitive guanine nucleotide-binding protein in the alpha1-adrenoceptor-mediated positive inotropic effect in the heart
Pertussis toxin, which specifically inactivates guanine nucleotide-binding proteins (N-proteins) involved in the signal transduction in various receptor systems, did not influence the positive inotropic effect...
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Article
Increased sensitivity to α-adrenoceptor stimulation but intact purinergic and muscarinergic effects in prehypertensive cardiac hypertrophy of spontaneously hypertensive rats
The effects of phenylephrine, isoprenaline and adenosine, (−)-N6-phenylisopropyladenosine (PIA) or carbachol alone and in the presence of isoprenaline on force of contraction were studied in isolated electrically...
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Article
Role of guanine nucleotide-binding protein in the regulation by adenosine of cardiac potassium conductance and force of contraction. Evaluation with pertussis toxin
In atrial cardiac preparations adenosine exerts a receptor-mediated negative inotropic effect due to an increased potassium conductance. Pretreatment of guinea pigs with pertussis toxin abolished the negative ...
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Article
Evidence for adenosine receptor-mediated isoprenaline-antagonistic effects of the adenosine analogs PIA and NECA on force of contraction in guinea-pig atrial and ventricular cardiac preparations
The effects of the adenosine agonists (−)-N6-phenylisopropyladenosine (PIA) and 5′-N-ethylcarboxamideadenosine (NECA) on force of contraction, adenylate cyclase activity and normal as well as slow action potentia...
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Article
Positive inotropic effect of bay K 8644: cAMP-independence and lack of inhibitory effect of adenosine
The aim of the present study was to characterize the positive inotropic effect of the Ca2+ channel activator Bay K 8644. In isolated guinea-pig papillary muscles we investigated whether adenosine and the R site a...