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10.1111/bph.13286 http://scihub22266oqcxt.onion/10.1111/bph.13286 C4687809!4687809!26282717     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Pharmacol 2015 ; 172 (21): 5199-210 Nephropedia Template TP {{tp|p=26282717|t=2015. The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood |pdf=|usr=}}{{26282717}} gab.com Text The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26282717 #FOAvip Background and Purpose: Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function. Experimental Approach: The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC?specific effects of riociguat were determined by comparing wild?type and platelet?specific sGC?knockout mice. Key Results: Riociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC?knockout platelets were not inhibited by riociguat. In washed human platelets, 100?nM riociguat reduced ADP?induced GPIIb/IIIa activation, while a 10?fold higher concentration was required to reduce convulxin?stimulated GPIIb/IIIa activation. Riociguat inhibited ADP?induced platelet shape change and aggregation, while ATP?induced shape change remained unaffected. However, in PRP and whole blood, 50?100??M riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood. Conclusions and Implications: Riociguat inhibits platelet activation in whole blood only at concentrations above 50??M, while the plasma concentrations in riociguat?treated patients are 150 to 500?nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered. Twit Text FOAVip The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26282717 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26282717 #FOAvip English Wikipedia <ref>{{Cite pmid|26282717}}</ref> The sGC stimulator riociguat inhibits platelet function in washed platelets but not in whole blood #MMPMID26282717 Reiss C; Mindukshev I; Bischoff V; Subramanian H; Kehrer L; Friebe A; Stasch J; Gambaryan S; Walter U Br J Pharmacol 2015[Nov]; 172 (21): 5199-210 PMID26282717show ga Background and Purpose: Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function. Experimental Approach: The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC?specific effects of riociguat were determined by comparing wild?type and platelet?specific sGC?knockout mice. Key Results: Riociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC?knockout platelets were not inhibited by riociguat. In washed human platelets, 100?nM riociguat reduced ADP?induced GPIIb/IIIa activation, while a 10?fold higher concentration was required to reduce convulxin?stimulated GPIIb/IIIa activation. Riociguat inhibited ADP?induced platelet shape change and aggregation, while ATP?induced shape change remained unaffected. However, in PRP and whole blood, 50?100??M riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood. Conclusions and Implications: Riociguat inhibits platelet activation in whole blood only at concentrations above 50??M, while the plasma concentrations in riociguat?treated patients are 150 to 500?nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered. äThe sGC stimulator riociguat inhibits platelet function in washed plat(epmc).pdf DeepDyve Pubget Overpricing