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10.1111/bph.12647 http://scihub22266oqcxt.onion/10.1111/bph.12647 C4294032!4294032 !24547784     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24547784 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Pharmacol 2014 ; 171 (23 ): 5169-81 Nephropedia Template TP {{tp|p=24547784 |t=2014. Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart |pdf=|usr=}}{{24547784 }} gab.com Text Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24547784 #FOAvip BACKGROUND AND PURPOSE: Levosimendan is known as a calcium sensitizer, although it is also known to inhibit PDE3. We aimed to isolate each component and estimate their contribution to the increased cardiac contractility induced by levosimendan. EXPERIMENTAL APPROACH: Contractile force was measured in electrically stimulated ventricular strips from explanted failing human hearts and left ventricular strips from normal male Wistar rats. PDE activity was measured in a two-step PDE activity assay on failing human ventricle. KEY RESULTS: Levosimendan exerted a positive inotropic effect (PIE) reaching maximum at 10(-5) ?M in ventricular strips from failing human hearts. In the presence of the selective PDE3 inhibitor cilostamide, the PIE of levosimendan was abolished. During treatment with a PDE4 inhibitor and a supra-threshold concentration of isoprenaline, levosimendan generated an amplified inotropic response. This effect was reversed by ?-adrenoceptor blockade and undetectable in strips pretreated with cilostamide. Levosimendan (10(-6) ?M) increased the potency of ?-adrenoceptor agonists by 0.5 log units in failing human myocardium, but not in the presence of cilostamide. Every inotropic response to levosimendan was associated with a lusitropic response. Levosimendan did not affect the concentration-response curve to calcium in rat ventricular strips, in contrast to the effects of a known calcium sensitizer, EMD57033 [5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one]. PDE activity assays confirmed that levosimendan inhibited PDE3 as effectively as cilostamide. CONCLUSIONS AND IMPLICATIONS: Our results indicate that the PDE3-inhibitory property of levosimendan was enough to account for its inotropic effect, leaving a minor, if any, effect to a calcium-sensitizing component. Twit Text FOAVip Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24547784 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24547784 #FOAvip English Wikipedia <ref>{{Cite pmid|24547784 }}</ref> Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart #MMPMID24547784 Orstavik O ; Ata SH ; Riise J ; Dahl CP ; Andersen GØ ; Levy FO ; Skomedal T ; Osnes JB ; Qvigstad E Br J Pharmacol 2014[Dec]; 171 (23 ): 5169-81 PMID24547784 show ga BACKGROUND AND PURPOSE: Levosimendan is known as a calcium sensitizer, although it is also known to inhibit PDE3. We aimed to isolate each component and estimate their contribution to the increased cardiac contractility induced by levosimendan. EXPERIMENTAL APPROACH: Contractile force was measured in electrically stimulated ventricular strips from explanted failing human hearts and left ventricular strips from normal male Wistar rats. PDE activity was measured in a two-step PDE activity assay on failing human ventricle. KEY RESULTS: Levosimendan exerted a positive inotropic effect (PIE) reaching maximum at 10(-5) ?M in ventricular strips from failing human hearts. In the presence of the selective PDE3 inhibitor cilostamide, the PIE of levosimendan was abolished. During treatment with a PDE4 inhibitor and a supra-threshold concentration of isoprenaline, levosimendan generated an amplified inotropic response. This effect was reversed by ?-adrenoceptor blockade and undetectable in strips pretreated with cilostamide. Levosimendan (10(-6) ?M) increased the potency of ?-adrenoceptor agonists by 0.5 log units in failing human myocardium, but not in the presence of cilostamide. Every inotropic response to levosimendan was associated with a lusitropic response. Levosimendan did not affect the concentration-response curve to calcium in rat ventricular strips, in contrast to the effects of a known calcium sensitizer, EMD57033 [5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one]. PDE activity assays confirmed that levosimendan inhibited PDE3 as effectively as cilostamide. CONCLUSIONS AND IMPLICATIONS: Our results indicate that the PDE3-inhibitory property of levosimendan was enough to account for its inotropic effect, leaving a minor, if any, effect to a calcium-sensitizing component. |Adrenergic beta-Agonists/pharmacology [MESH] |Animals [MESH] |Calcium/physiology [MESH] |Cardiotonic Agents/*pharmacology [MESH] |Heart Failure/*physiopathology [MESH] |Heart/physiopathology [MESH] |Humans [MESH] |Hydrazones/*pharmacology [MESH] |In Vitro Techniques [MESH] |Isoproterenol/pharmacology [MESH] |Male [MESH] |Milrinone/pharmacology [MESH] |Myocardial Contraction/drug effects [MESH] |Phosphodiesterase 3 Inhibitors/*pharmacology [MESH] |Phosphodiesterase 4 Inhibitors/pharmacology [MESH] |Pyridazines/*pharmacology [MESH] |Quinolines/pharmacology [MESH] |Quinolones/pharmacology [MESH] |Rats, Wistar [MESH] |Rolipram/pharmacology [MESH] |Simendan [MESH]Inhibition of phosphodiesterase-3 by levosimendan is sufficient to acc(epmc).pdf DeepDyve Pubget Overpricing