抄録
The interactions between platelets and vascular walls have special significance for atherosclerotic heart disease. The aims of this study were to determine whether atherosclerosis is associated with altered vascular reactivity to aggregating platelets and to elucidate the responsible underlying mechanisms. Isolated helical strips of aortae and coronary arteries from age-matched control and Watanabe Heritable Hyperlipidemic rabbits (WHHL rabbits) (average age=10 months for aortic study and 22 months for coronary study) were mounted for isometric tension recording in oxygenated buffer. All the segments of aortae and coronary arteries from WHHL rabbits showed atherosclerotic lesions macroscopically. Cumulative additions of suspended platelets (104-3×106/μl) activated with thrombin into the organ bath resulted in platelet count-related aortic contractions. The maximum serotonin (5HT) and thromboxane (TX) B2 concentration in the bath solution averaged 148 ng/ml and 24 ng/ml. Contractile responses of atherosclerotic aortae to aggregating platelets were markedly augmented as compared to controls. An incubation of platelets with aspirin, which completely inhibited TX A2 synthesis without any alterations of 5HT release, did not attenuate hyperreactivity of atherosclerotic aortae compared to controls. Prior exposure to phentolamine or diphenhydramine also did not alter contractile responses to aggregating platelets. The treatment of aortic strips with methysergide inhibited responses to aggregating platelets in both atherosclerotic and control groups, indicating a serotonergic mechanism of its hyperreactivity. To further elucidate its responsible mechanism, contractile responses to exogenously administered 5HT, histamine and TX A2 were examined in aortic strips from control and WHHL rabbits. Responsiveness of atherosclerotic aortae to 5HT was significantly augmented compared to controls. There were no differences in the responses to histamine between two groups. Atherosclerotic aortae exhibited impaired responses to TX A2 prepared by incubation of PG H2 with calf platelet microsomes or ST A2, a stable TX-like analogue, as compared to controls. These results also can help to explain the mechanisms responsible for hyperreactivity of atherosclerotic aortae to aggregating platelets.
In addition, atherosclerotic coronary arteries exhibited a markedly enhanced reactivity to aggregating platelets and 5HT.
