Effects of propranolol therapy on platelet release and prostaglandin generation in patients with coronary heart disease.
Suppression of platelet function is thought to be a mechanism of propranolol's beneficial action in angina pectoris. To study the effects of propranolol on platelets, we measured plasma beta thromboglobulin and plasma thromboxane B2 (TXB2, stable metabolite of TXA2) levels by radioimmunoassay as indexes of platelet alpha-granule and TXA2 release, respectively. Platelet TXA2 generation in vitro in response to arachidonate and thrombin was also quantitated. Twenty-nine patients with coronary disease -- 15 not taking propranolol (group A) and 14 taking propranolol (group B) -- and 15 normal subjects were studied. Plasma beta-thromboglobulin levels were increased in group A and B patients (mean 63 +/- 8 and 96 +/- 14 ng/ml, respectively) compared with normal subjects (mean 46 +/- 6 ng/ml). Plasma TXB2 levels were similar in group A and B patients and in normal subjects (mean 148 +/- 41, 149 +/- 36 and 216 +/- 39 pg/ml). Arachidonate-induced platelet TXA2 generation was significantly higher in group A patients than in normal subjects (725 +/- 393 vs 82 +/- 25 pg TXB2/10(8) platelets, p less than 0.001). In contrast, platelets from group B patients had very low TXA2 generation (mean 21 +/- 18 pg) compared with platelets from group A patients or normal subjects (p less than 0.001). Similar results were obtained using thrombin. These data show that propranolol therapy does not affect platelet-released beta thromboglobulin or TXA2 at rest, but significantly reduces the capability of platelets to generate TXA2 in vitro. Reduction in platelet TXA2 generation may be an important mechanism of action of propranolol in patients with coronary artery disease.
D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D003864:Depression, Chemical; D006801:Humans; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D011453:Prostaglandins / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D001620:beta-Thromboglobulin / Q000032:analysis
D001095:Arachidonic Acids; D011453:Prostaglandins; D001620:beta-Thromboglobulin; D013929:Thromboxane B2; D013928:Thromboxane A2; D011433:Propranolol; D013917:Thrombin