Platelets and blood vessels.
The intravascular adhesion and aggregation of platelets initiate hemostasis and arterial thrombosis. In vitro, platelet aggregation is induced by many different agents; which of these is responsible for aggregation in vivo is now under investigation. For this purpose, we have developed novel techniques for the reproducible determination of bleeding times in mesenteric arterioles of rats and rabbits. Local infusions of enzyme systems which remove adenosine diphosphate (ADP) greatly increase the bleeding time at arterial injuries distal to the site of infusion. These observations establish the involvement of ADP in the activation of platelets for primary hemostasis. Direct measurement of free adenosine triphosphate (ATP), as an indicator of ADP, at such injury sites indicates that enough ADP for activating platelets is released very rapidly from damaged vessel walls and much later from the platelets themselves. This bleeding-time technique has also shown that hemostatic platelet aggregation is delayed less by the inhibition of the production of thromboxane A2 than by that of ADP. These observations provide an explanation for the ineffectiveness of any simple platelet-inhibiting drug (including aspirin) by itself, whenever arterial (e.g., coronary or cerebral) thrombosis is initiated by hemorrhages into atheromatous plaques. On the other hand, aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischemia. This partial effectiveness can be explained by an action of aspirin on platelets, assuming that, in such cases, their thromboembolic aggregation is initiated by hemodynamic effects of atheromatous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology*; D001808:Blood Vessels / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D010973:Platelet Adhesiveness; D013927:Thrombosis / Q000503:physiopathology
D000244:Adenosine Diphosphate