Inhibition of platelet aggregation by polyaspartoyl L-arginine and its mechanism.
OBJECTIVE
To observe the oral anti-platelet efficacy and the potential action mechanism of polyaspartoyl L-arginine (PDR), a new L-arginine rich compound.


METHODS
Platelet aggregation was conducted by Born's method; bleeding time was determined using tail's bleeding time in mice; platelet adhesion was carried out with glass bottle method; nitric oxide (NO) was tested with Griess's method; and cAMP, thromboxane B(2) (TXB(2)) and 6-keto-PGF(1 alpha ) were assessed with commercial kits.


RESULTS
The inhibition by PDR (15-60 mg/kg i.g. or 10 mg/kg i.v.) of platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin at 1 h after oral administration or at 20 min after i.v. injection for rats (P<0.01), and its (15 mg/kg, i.g.) inhibition of ADP-induced platelet aggregation for rabbits during 6 h after administration were observed. PDR (15-60 mg/kg) prolonged the bleeding time of mice (P<0.05) and (30 mg/kg) increased NO concentration in plasma. On the other hand PDR did not change the contents of cAMP in platelet and TXB2 or 6-keto-PGF(1 alpha) in plasma.


CONCLUSIONS
PDR is a novel, oral effective platelet aggregation inhibitor and its action mechanism possibly related to increasing NO generation.
Wang
Yin-ye
YY
Department of Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China. wangyinye@bjmu.edu.cn
Tang
Zhi-yu
ZY
Dong
Min
M
Liu
Xiao-yan
XY
Peng
Shi-qi
SQ
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000097:blood*; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000097:blood
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C483710:polyaspartoyl-L-arginine; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000242:Cyclic AMP