title: Increased plasma level of asymmetric dimethylarginine in hypertensive rats facilitates platelet aggregation: role of plasma tissue factor.
abstract: This study was designed to explore the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in platelet aggregation in hypertension and its possible mechanisms. Spontaneously hypertensive rats (SHR) and L-NAME-induced hypertensive rats were orally administered with L-arginine (1 g/(kg·day) for 14 days. Systolic blood pressure, platelet aggregation, and plasma tissue factor (TF) level and activity were measured. The plasma concentration of ADMA in SHR was determined. In vitro, platelet-rich plasma isolated from Wistar rats was prepared in order to observe the effect of exogenous ADMA on platelet aggregation and TF level and (or) activity in platelet-rich plasma. In both types of hypertensive rats, systolic blood pressure, platelet aggregation, and the level and activity of plasma TF were elevated compared with corresponding control animals. Plasma ADMA level was also increased in SHR. Treatment with L-arginine, a competitor of ADMA, lowered blood pressure and inhibited platelet aggregation concomitantly with a decrease in plasma TF level and activity in both types of hypertensive rats. We also found that exogenous ADMA promoted platelet aggregation and increased TF level and (or) activity in platelet-rich plasma, an effect that was inhibited by pretreatment with L-arginine. Importantly, the enhanced platelet aggregation induced by exogenous ADMA was reduced by pretreatment with anti-TF antibody. The results suggest that endogenous ADMA may be involved in platelet hyperaggregation status in hypertension, and the facilitation of platelet aggregation by ADMA is related to upregulation of the level and activity of plasma TF.
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.forename: Ren
authors.initials: R
authors.lastname: Guo
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Chen
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D013925:Thromboplastin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C018524:N,N-dimethylarginine; D013925:Thromboplastin; D001120:Arginine