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Increased plasma level of asymmetric dimethylarginine in hypertensive rats facilitates platelet aggregation: role of plasma tissue factor
Update time:2018-11-09 09:37:00   【 Font: Large  Medium Small

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/(kgday) 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.

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Source:canadian journal of physiology and pharmacology      by Dai Li Ren Guo Qing-Quan Chen Chang-Ping Hu Xiang Chen
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