Effects Of Ramipril On Platelet Function And Hemorheology In Rats With Acute Blood Stasis Model

Effects of Ramipril on platelet function and hemorheology in rats with acute blood stasis modelCoronary atherosclerotic heart disease is a kind of disease which is caused by blood vessel stenosis or occlusion after coronary atherosclerosis, or by myocardial ischemia, hypoxia or necrosis induced in coronary artery functional changes. As people life style changes, and working rhythm, cerebrovascular disease speed increasingly serious bothering people's normal life and work. Our cerebrovascular disease incidence and associated risk factors present increasing trend of urban and rural residents in China, the first cause, the increasing incidence, greater harm to people and countries, bring great social and economic burden. Although there are many clinical therapeutic drugs, but related to coronary heart disease prevention, far from ideal, and the effect is satisfied. Urgent demand side effects, therapeutic effect significantly, economical and practical, and can be widely used in the clinical treatment of coronary heart disease.Angiotensin-converting enzyme (ACE) inhibitors have become one of the preferred drugs in the treatment of hypertension and heart failure, and it is also widely used in clinical treatment of acute myocardial infarction, diabetic nephropathy, cardiovascular remodeling, as well as diseases such as atherosclerosis. Ramipril is a new potent and long-acting ACE inhibitor, as a prodrug, it could be absorbed through the gastrointestinal tract, and was hydrolyzed into an active amiprilat in the liver, by playing the role of competitive inhibition of ACE. At present, the clinical indications Ramipril is limited to essential hypertension and the light-moderate heart failure after acute myocardial infarction. Whether ramipril could inhibit platelet function and could improve blood viscosity has not been reported.In this paper, a acute blood stasis model in rats would be used and the platelet adhesion, aggregation,blood rheology changes are observed and the role of Ramipril in promoting blood circulation will be evaluated to provide experimental evidence for expanding its clinical application.50 healthy Wistar rats were selected, and were randomly divided into five groups:the normal control group, acute blood stasis model group, Ramipril 0.5,1,2 mg/kg group. Drug group gavageltime a day, continuous 6days, the normal control group and acute blood stasis model group were given equal volume of 0.5%sodium carboxymethyl cellulose.On the 6th day,30min after administration, the rats (without the rats in normal control group) were injected 0.1%adrenaline 0.8mL/kg,2h later rats were immersed in ice water for 5min,2 h later by 0.6 mL/kg injection of a 0.1%epinephrine to form the acute blood stasis model. No.7d,1 h after administration, each animal is anesthetized using sodium pentobarbital (30mg/kg i.p.), abdominal aortic blood, blood taken were taken from abdominal aortic, and heparin used for anticoagulation.1 mL of blood was taken from the additions of 4 mL of whole blood anticoagulant and added in to LBY-N6A rotational viscometer, and tested for the whole blood viscosity (10/s,40/sand 160/s), the remaining 3 mL of whole blood was taken to centrifuge (3000r/min 10min),1 mL of the upper plasma was taken into the viscometer (120/s); plasma PGI2 and TXA2 was measured using the remaining plasma by radioimmunoassay, the concentration of plasma fibrinogen (Fib) was measured by microcalorimetry precipitation. Abdominal aortic blood sampling 1mL, with 3.8%sodium citrate according to 1:9 ratio of anticoagulant, 1000r centrifuge d for 10min, added 20μL of plasma to 380μL of platelet-dilution liquid, mix, trickle-down into cell count board, it was put aside for 10min. Platelet was counted under the optical microscope.The remaining blood was added to the spherical glass of LBY-5F platelet adhesion instrument and rotated at 3.7r/min for 15min. After the adhesion,20μL of the plasma was counted under microscopy using cell count board, and platelet adhesion (PA) was calculated. Abdominal aortic blood sampled 1.5 mL, anticoagulant with 3.8%sodium citrate according to 1:9 ratio, mixied,1500r/min centrifugal for 5min, the supernatant obtained was the platelet-rich plasma (PRP).200μL of the PRP was Placed into colorimetric cup with stirrer, the cup was then placed in the thermostat behind. The remaining anti-coagulated blood was taken to 3000r/min centrifugal for 10min, the supernatant was platelet-poor plasma obtained (PPP). 300μL of the PPP was injected into the colorimetric cup, placed in test holes,after the automatic 0 detection, the PPP cup was removed and replaced by inserting the PRP cup. 11μL of the well-prepared platelet aggregation agent adenosine diphosphate (ADP) quickly pushed into the tested samples using a micro-injector along the cuvette into the bottom corner, platelet aggregation activity was tested by LBY-NJ2 platelet aggregation instrument using turbidimetry. The platelet aggregation (PAG) at 1,3,5 min and maximum platelet aggregation rate (MPAG) were calculated. Hematocrit (Hct) was tested using micro-capillary tube method; RBC electrophoresis time (RCET) was tested by XN3-type RBC electrophoresis timer; also the erythrocyte sedimentation rate(ESR). Finally, the erythrocyte aggregation index (EAI) and erythrocyte rigidity index (ERI).The results showed that Ramipril can significantly reduce whole blood viscosity, plasma viscosity and plasma thromboxane A2 (TXA2) levels in acute blood stasis model rats, and significantly inhibited the activity of platelet adhesion and aggregation. Also, we could see from the results that the concentration of plasma fibrinogen (Fib), erythrocyte sedimentation rate (ESR), hematocrit (Hct), erythrocyte aggregation index (EAI) and erythrocyte rigidity index (ERI) were significantly lowered. Plasma prostacyclin (PGI2) and PGI2/TXA2 ratio was markedly highered and the red blood cell electrophoretic time (RCET) was shortened evidently. That means blood viscosity, platelet adhesion and aggregation function and abnormal blood rheology changes in acute blood stasis rat model are significantly improved, which could help avoid high blood pressure, high-viscosity state in acute myocardial infarction, and are beneficial to the prevention of thrombosis, the occurrence and development of atherosclerosis.