Low-dose aspirin inhibits platelet-induced contraction of the human isolated coronary artery. A role for additional 5-hydroxytryptamine receptor antagonism against coronary vasospasm?
BACKGROUND
The beneficial effect of low-dose aspirin in the prevention of coronary vasospasm is well documented. In this study, we investigated the contractile effect of human washed platelets on the human isolated coronary artery. We concentrated on the effect of low-dose aspirin (40 mg/d) taken by the platelet donor and on the efficacy of thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT) receptor antagonists.


RESULTS
Human coronary artery segments were suspended in an organ bath set-up for isometric tension measurement. Platelets (10(9) to 3 x 10(10)/L) elicited concentration-dependent contractile responses of the coronary artery segments, reaching 28.4 +/- 7.1% of contractions induced by 100 mmol/L K+. The contractile response tended to be decreased in vessel segments with histological signs of early atherosclerosis. Contraction was significantly attenuated after pretreatment of the vessel segments with ketanserin (5-HT2 receptor antagonist, 1 mumol/L) or SQ30741 (TXA2 receptor antagonist, 0.01 mumol/L), reaching 8.8 +/- 2.3% and 3.2 +/- 2.2% of contraction to 100 mmol/L K+, respectively. Platelets obtained from the same platelet donors after they had taken aspirin (40 mg/d for 7 to 13 days) caused significantly lower contractile responses (7.6 +/- 2.7% of 100 mmol/L K+) associated with an almost selective inhibition of the synthesis of thromboxane measured in the organ bath solution (untreated platelets, 2.19 +/- 0.43 nmol/L; aspirin-treated platelets, 0.66 +/- 0.05 nmol/L). The amount of 5-HT secreted in the organ bath remained unaltered (65.17 +/- 9.94 and 64.03 +/- 8.98 nmol/L, respectively). This explains why ketanserin significantly attenuated the residual contractile responses caused by platelets obtained from aspirin-treated subjects, whereas SQ30741 caused minor, nonsignificant additional attenuation.


CONCLUSIONS
The results of the present study therefore suggest that additional antagonism of the contractile 5-HT receptors in the coronary artery may increase the efficacy of low-dose aspirin in vivo.
Bax
W A
WA
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Renzenbrink
G J
GJ
van der Linden
E A
EA
Zijlstra
F J
FJ
van Heuven-Nolsen
D
D
Fekkes
D
D
Bos
E
E
Saxena
P R
PR
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002648:Child; D003329:Coronary Vasospasm / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists
D015777:Eicosanoids; D012702:Serotonin Antagonists; D012701:Serotonin; D001241:Aspirin