OS 32-09 THE BENEFICIAL EFFECT OF LOSARTAN ON PLATELET AGGREGATION RESULTS FROM THE REDUCTION OF ENDOGENOUS ASYMMETRIC DIMETHYL ARGININE IN SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Objective: Previous studies show that platelet aggregation and asymmetric dimethyl arginine (ADMA) are increased in hypertensive patients and animals. However, the relationship between endogenous ADMA and platelet aggregation in spontaneous hypertensive rats (SHR) remains unclear. Since Losartan can increase the nitric oxide (NO) release and ameliorate the state of thrombosis, we aimed to test whether the beneficial effect of losartan on platelet aggregation results from the reduction of ADMA generation. Design and Method: With male Wistar Kyoto rats (WKY) as normal control, we randomly divided male SHR into three groups: SHR control group, L-arginine-treated (1.0 g/kg) and losartan-treated (30 mg/kg) group. For each group, we measured systolic blood pressure (SBP), platelet aggregation rate (pt-Ag), NO level, NOS activity and ADMA content in both plasma and platelets. Results: Compared with WKY rats, the ADMA level in both plasma and in platelets and platelet aggregation rate in SHR were higher, while the NO level and NOS activity were lower. L-arginine (1.0 g/kg) and losartan (30 mg/kg) treatment decreased platelet aggregation rate concomitantly with the decreased level of ADMA and the increased level of NO and the activity of NOS. Incubating platelets from SD rats with thoracic aortic rings for 5 min, the platelet aggregation rate in SHR was higher than that of WKY rats. L-arginine (1.0 g/kg) and losartan (30 mg/kg) significantly reduced the platelet aggregation rate. Conclusions: Our results suggest that endogenous ADMA plays a key role in platelet aggregation, and the beneficial effect of losartan is related to the reduced ADMA level.