[Effect of asymmetric dimethylarginine on platelet-aggregation and losartan intervention in spontaneous hypertensive rat models].
OBJECTIVE
To evaluate the effect of asymmetric dimethylarginine (ADMA) and the results of losartan intervention on platelet-aggregation in spontaneous hypertensive rats.


METHODS
Spontaneous hypertensive rats (SHR) were randomly assigned into 3 groups: SHR control group, L-arginine treatment group (L-arg) and losartan (los) treatment group, each group consisting of 16 rats. Another 16 Wistar Kyoto rats (WKY) served as normal control group. The L-arginine and losartan treatment groups received 1.0 g/kg L-arginine or 30 mg/kg losartan in 10 mL/kg distilled water daily through gastric tube for 2 weeks respectively, while the SHR and WKY groups received distilled water alone. All the rats took tap water and standard feed freely during the experimental period. Systolic blood pressure (SBP) was monitored by the tail-cuff method. At the end of the 2-week intervention, all the rats were sacrificed and the blood samples were collected from the carotid artery. The platelet-aggregation-rate, NO levels, eNOS activity, and ADMA levels both in the plasma and the platelets were measured. We got other platelet samples from the SD rats and incubated the platelets with blood vascular endothelium from the above 4 groups of experimental rats and the platelet-aggregation-rate was monitored as well.


RESULTS
(1) Systolic blood pressure of the SHR was significantly higher, compared with that of the WKY (P<0.01), which were significantly reduced both in the L-arginine and losartan groups (P<0.01). (2) Platelet-aggregation-rate of the SHR was significantly higher, compared with that of WKY (P<0.01), which was significantly reduced both in the L-arginine and losartan groups (P<0.01). (3) NO levels both in the plasma and the platelets of the SHR were lower, compared with those of the WKY (P<0.05); and were elevated significantly both in the L-arginine and losartan groups,compared with those of the SHR (P<0.05); (4) Both the plasma and the platelet eNOS activities of SHR followed the same pattern of the NO levels in these groups (P<0.01). (5) In contrast, the plasma and platelet ADMA levels showed a reverse pattern (P<0.05). (6) Platelets from the SD rats incubated with vascular endothelium of WKY exhibited lower platelet-aggregation-rate,compared with the platelets incubated with SHR vascular endothelium (P<0.05); Platelet-aggregation-rate of the SHR group increased, compared with that of the WKY group (P<0.05); Platelet-aggregation-rate both of L-arginine and losartan groups reduced, compared with that of the SHR group (P<0.05).


CONCLUSIONS
High levels of ADMA both in the plasma and in the platelets of SHR are associated with the decline of eNOS activity and NO levels, which might be an important reason for the increased platelet-aggregation-rate. Intervention with Losartan can reduce the platelet-aggregation-rate simultaneously with its known anti-hypertensive effect. The possible mechanism might be that losartan can enhance the eNOS activity and elevate NO levels through the suppression of ADMA.
Xia
Ke
K
Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410078, China.
Li
Dai
D
Zhao
Zhen-yu
ZY
Yang
Tian-lun
TL
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; C018524:N,N-dimethylarginine; D001120:Arginine; D019808:Losartan