Response of human coronary arteries to aggregating platelets: importance of endothelium-derived relaxing factor and prostanoids.
Epicardial human coronary arteries (HCA) were obtained during heart transplantation. Strip preparations were mounted for isometric tension recording. Tension was induced with prostaglandin F2 alpha (0.3-3 microM). Aggregating human platelets (10(7)/ml and 10(8)/ml) caused marked relaxation if the endothelium of the HCA was intact, but produced modest additional constriction if the endothelium was removed. The endothelium-dependent relaxations to platelets were slightly enhanced in the presence of methysergide (1 microM) or after treatment of the platelets with the thromboxane synthase inhibitor dazmegrel (1 mM, 30 minutes). Relaxations to platelets were markedly inhibited or abolished in the presence of apyrase (1 unit/ml), after selective pretreatment of HCA with gossypol or methylene blue (both 30 microM, 30 minutes), or after addition of hemoglobin (20 microM) to the organ bath. Pretreatment of HCA (not the platelets) with aspirin (30 microM, 30 minutes) had no significant effect on platelet-induced relaxations. Adenosine 5'-diphosphate (0.1-100 microM) induced marked relaxations in endothelium-intact and much smaller relaxations in endothelium-denuded HCA. A low concentration (10 nM) of serotonin (5-HT) produced modest endothelium-dependent relaxations, higher concentrations (0.1-1 microM) led to increases in tension (also in the presence of endothelium). The thromboxane A2 mimetic U44069 (1-100 nM) was the most potent constrictor of HCA irrespective of the presence or absence of endothelium. After inhibition of thromboxane synthase, platelets produced large amounts of prostaglandins E2 and F2 alpha. Both prostaglandins constricted HCA, which can explain the limited effects of dazmegrel.(ABSTRACT TRUNCATED AT 250 WORDS)
Förstermann
U
U
Department of Clinical Pharmacology, Hannover Medical School, FRG.
Mügge
A
A
Bode
S M
SM
Frölich
J C
JC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001688:Biological Products / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide; D010974:Platelet Aggregation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D001688:Biological Products; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D009569:Nitric Oxide; D012701:Serotonin; D000244:Adenosine Diphosphate