Abstract:
:In the presence of 3-isobutyl-methylxanthine (IBMX), induction of cyclic 3',5'-guanosine monophosphate (GMP) production in human washed platelets (HWP) by nitric oxide donors (NOD) is followed by its accumulation in the surrounding medium in a time- and concentration-dependent manner. Thirty minutes incubation of HWP with 3-morpholino-sydonimine (SIN-1, 10 microM) at 37 degrees C resulted in a 4.6-fold increase of cyclic GMP in platelets, whereas in the extracellular medium the increase was 17.6-fold. Similar results were obtained when other NOD such as S-nitroso-N-acetylpenicyllamine (SNAP) and 3-(2-methoxy-5-chlorophenyl)oxatriazol-5-imine (GEA 3184) and the selective phosphodiesterase inhibitor, zaprinast (M&B 22948, 10 microM), were used. Probenecid (1-300 microM), an inhibitor of organic anion transport, or ouabain (1-300 microM), an inhibitor of Na+/K+ adenine triphosphate (ATP)-ase had no effect on cyclic GMP production or extrusion after stimulation with SIN-1. Significantly prostaglandin A1 (PGA1) and prostaglandin D2 (PGD2) inhibited the efflux of cyclic GMP from platelets induced by SNAP (10 microM) in a concentration-dependent fashion, with an IC50 of 63 +/- 16 and 143 +/- 17 microM, respectively. These studies suggest that the extrusion of cyclic GMP from human platelets after activation of soluble guanylate cyclase by NOD may contribute to the control of cyclic GMP levels in platelets with potential physiological and therapeutic consequences.
journal_name
Int J Cardioljournal_title
International journal of cardiologyauthors
Radziszewski W,Chopra M,Zembowicz A,Gryglewski R,Ignarro LJ,Chaudhuri Gdoi
10.1016/0167-5273(95)02427-xsubject
Has Abstractpub_date
1995-10-01 00:00:00pages
211-20issue
3eissn
0167-5273issn
1874-1754pii
016752739502427Xjournal_volume
51pub_type
杂志文章abstract::In a press conference on Nov. 20, 2001 it was announced that the Multi-center Autonomic Defibrillator Implantation Trial II (MADIT II) was stopped early because of a 30% reduction in mortality in patients randomised to receive an implantable defibrillator device. The 4 year multi-centre trial of 1200 patients was term...
journal_title:International journal of cardiology
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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