الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
The present work was planned to study the hemostatic changes associated with aging and to explore the effect of NO on hemostasis in adult and old rats. In addition, the potential antithrombotic action of the NO donor, L-arginine was investigated. The effect of NO deficiency, induced by L-NAME, was also assessed.
This study was performed on Wistar albino rats of both sexes, divided into 2 main groups:
Group I: Adult group, 12 month old (n= 92)
Group II: Old group, 24 month old (n=104)
Rats in each of the 2 main groups were categorized into male groups and female groups. Each of the adult male, adult female, old male and old female groups was further subdivided into:
- Control groups received distilled water by gavage daily for 2 weeks.
- L-arginine-treated groups received the nitric oxide donor, L-arginine, by gavage in a dose of 100 mg/ml/kg body weight, daily for 2 weeks.
- L-NAME-treated groups received the nitric oxide synthase inhibitor, L-NAME, by gavage in a dose of 20 mg/ml/kg body weight, daily for 2 weeks.
Blood samples from all these groups were subjected to the determination of plasma nitrate level, prothrombin time, activated partial thromboplastin time, platelet count, platelet aggregation, and plasma fibrinogen degradation products, as well as complete blood count, plasma lipid profile and plasma alanine aminotransferase.
The encountered results revealed that aging was associated with a lower plasma nitrate level in male and female rat groups. The decreased plasma NO levels was associated with higher platelet count in male and female rat groups and enhanced platelet aggregation in male rats only. However, aging did not affect the coagulation system or the fibrinolytic system in either male or female groups. Higher neutrophil/lymphocyte ratio, lower plasma HDL and higher plasma LDL levels were observed in old rat groups of both male and female sexes. It is worth noting that the enhanced platelet aggregation observed in old male rats was associated with higher hematocrit values. Plasma ALT levels were not affected by aging in either of male and female groups.
L-arginine administration to old rats increased their plasma nitrate levels. This increase was accompanied, in male group only, by reduction of ADP-induced platelet aggregation and increased plasma FDPs level. However, PT, APTT and platelet count were not changed significantly. In old male rats, the NO-induced reduction of platelet aggregation was associated with lowered erythrocyte parameters and normalized lipid profile. However, L-arginine administration did not affect neutrophil/lymphocyte ratio.
Although insignificant, the decrease in plasma nitrates following L-NAME administration to old male rats resulted in significant increase in platelet count. In old female rats, the decrease in plasma nitrates, upon L-NAME administration, was significant and resulted in increase in plasma TG, total cholesterol and LDL levels.
In adult rats, L-arginine treatment increased the plasma nitrates in male and female groups. However, in male rats, it did not affect the hemostatic parameters measured. In female rats, the resultant NO excess, shortened the PT, prolonged the APTT and increased the platelet count without affecting platelet aggregation. The changes encountered in plasma FDP levels were non-significant in either sex. NO excess, also, increased the plasma LDL level in the female group only, suggesting a mechanism for the shortened PT.
NO deficiency in adult rats exerted non-significant changes on hemoststic parameters apart from the increased platelet count in adult female rats. However, it increased the plasma LDL levels, which was accompanied, in female rats, by increased erythrocyte parameters and decreased HDL levels. NO deficiency, also, increased the levels of total cholesterol in adult males.
from this study, we can conclude that aging increases platelet aggregation in males but not in females with non-significant changes in coagulation or fibrinolysis. High hematocrit and disturbed plasma lipids in aged rats may precipitate NO deficiency which in turn contributes to the high thrombotic tendency.
L-arginine supplementation had beneficial effects on platelet aggregation in old males through increasing NO synthesis, without significant effects on coagulation or fibrinolysis.