PMID- 13678646
OWN - NLM
STAT- MEDLINE
DCOM- 20040812
LR  - 20191107
IS  - 1537-1891 (Print)
IS  - 1537-1891 (Linking)
VI  - 40
IP  - 3
DP  - 2003 Oct
TI  - Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase 
      activator, BAY 41-2272.
PG  - 149-54
AB  - Nitric oxide (NO) plays an important role in cardiovascular homeostasis, 
      particularly in the regulation of vascular tone and the reactivity of platelets 
      and circulating cells. Soluble guanylate cyclase (sGC) acts as the principal 
      biological target for NO and catalyses the formation of the intracellular second 
      messenger cyclic GMP (cGMP); activation of this enzyme is thought to be 
      responsible for the majority of cardiovascular actions of NO. In the present 
      study, we have evaluated the antiplatelet effects of a novel non-NO-based sGC 
      activator, BAY 41-2272, in vitro and in vivo. BAY 41-2272 produced a marked 
      inhibition of platelet aggregation in washed platelets with a potency (IC(50) 
      approximately 100 nM) some threefold less than the NO donor S-nitrosoglutathione. 
      BAY 41-2272 also prevented aggregation in platelet-rich plasma (PRP), albeit with 
      a much lower potency. Both NO and prostacyclin exhibited synergistic activity 
      with BAY 41-2272 to inhibit platelet aggregation. In vivo, at doses of BAY 
      41-2272 that significantly reduced blood pressure, the compound had little effect 
      on FeCl(3)-induced thrombosis. These data confirm that intraplatelet sGC 
      activation results in inhibition of aggregation and suggests that novel 
      non-NO-based sGC activators, which possess both hypotensive and antiplatelet 
      activities, may be useful as therapeutic agents.
FAU - Hobbs, Adrian J
AU  - Hobbs AJ
AD  - Wolfson Institute for Biomedical Research, University College London, Cruciform 
      Building, Gower Street, London WC1E 6AE, UK. a.hobbs@ucl.ac.uk
FAU - Moncada, Salvador
AU  - Moncada S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 
      (3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Chlorides)
RN  - 0 (Enzyme Activators)
RN  - 0 (Ferric Compounds)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - U38V3ZVV3V (ferric chloride)
SB  - IM
MH  - Adenosine Diphosphate/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Blood Pressure/drug effects
MH  - Carotid Artery Thrombosis/chemically induced/prevention & control
MH  - Chlorides
MH  - Cyclic GMP/metabolism
MH  - Enzyme Activators/*pharmacology
MH  - Epoprostenol/metabolism/pharmacology
MH  - Ferric Compounds
MH  - Guanylate Cyclase
MH  - In Vitro Techniques
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Platelet Aggregation/drug effects
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Pyrazoles/*pharmacology
MH  - Pyridines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Cytoplasmic and Nuclear/*biosynthesis
MH  - Soluble Guanylyl Cyclase
MH  - Time Factors
EDAT- 2003/09/19 05:00
MHDA- 2004/08/13 05:00
CRDT- 2003/09/19 05:00
PHST- 2003/09/19 05:00 [pubmed]
PHST- 2004/08/13 05:00 [medline]
PHST- 2003/09/19 05:00 [entrez]
AID - S1537189103000466 [pii]
AID - 10.1016/s1537-1891(03)00046-6 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2003 Oct;40(3):149-54. doi: 10.1016/s1537-1891(03)00046-6.