Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Weksler, Babette B.; Tack-Goldman, K; Subramanian, Valavanur A.; Gay, William A.

doi:10.1161/01.cir.71.2.332

Cited by 116 publications

(30 citation statements)

References 31 publications

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“…Thus, the present result implies that aspirin even at the low dose, which does not affect platelet aggregation, could at tenuate the ability of the endothelium to produce PGI2. Indeed, the same phenomenon was also observed in nor mal volunteers and patients with atherosclerosis (23,24). Cumulative administration of a low dose (3 mg/kg) aspi rin significantly attenuated the production of PGI2 by the cephalic (23) and the saphenous vein (24).…”

Section: Discussionsupporting

confidence: 61%

Effects of a Thromboxane A2-Receptor Antagonist, a Thromboxane Synthetase Inhibitor and Aspirin on Prostaglandin I2 Production in Endothelium-Intact and -Injured Aorta of Guinea Pigs

Higo

Karasawa

1994

Japanese Journal of Pharmacology

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ABSTRACT-We examined the effects of KW-3635, a thromboxane (TX) A2-receptor antagonist, and OKY-046, a TX synthetase inhibitor, on the prostaglandin (PG) 12 production in endothelium-intact and -in jured guinea pig aorta and compared them with those of aspirin. In the endothelium-intact aorta, both the low (3 mg/kg) and the high (100 mg/kg) dose of aspirin similarly reduced the PGI2 production, as measured ex vivo 1 hr after the injury. In contrast, neither KW-3635 (10 mg/kg) nor OKY-046 (30 mg/kg) inhibited the PGI2 production. The endothelial injury, induced by balloon catheterization, caused a reduction of PGI2 production in the aorta and decline of plasma PGI2/TXA2 ratio. In the endothelium-injured animals, the high dose of aspirin further reduced the PGI2 production in the aorta, whereas KW-3635 and OKY-046 did not affect it. KW-3635 and OKY-046 also ameliorated the reduced ratio of PGI2/TXA2 in the plasma. The present results demonstrate that aspirin, but not KW-3635 or OKY-046, reduces the PGI2 production in the aorta either in the endothelium-intact or -injured state. It is thus suggested that the TXA2-receptor an tagonist and the TX synthetase inhibitor have some advantages over aspirin when used for the prevention of acute thrombosis after percutaneous transluminal angioplasty.

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Section: Discussionsupporting

confidence: 61%

Effects of a Thromboxane A2-Receptor Antagonist, a Thromboxane Synthetase Inhibitor and Aspirin on Prostaglandin I2 Production in Endothelium-Intact and -Injured Aorta of Guinea Pigs

Higo

Karasawa

1994

Japanese Journal of Pharmacology

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“…Eight patients (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) years old) with type 1 diabetes from the endocrinology outpatient clinic at St. Boniface Hospital volunteered for the study. They fell into two subgroups: those with diabetes for less than 10 years having no complications of diabetes (n = 5) and those with diabetes for more than 10 years having proliferative retinopathy (n = 3).…”

Section: Subjects and Methods Drugsmentioning

confidence: 99%

“…An additional five controls (age, [24][25][26][27][28][29][30][31][32][33][34][35] years) were studied after the initial trial had been completed. These subjects were placed on 2 weeks of single dose 325 mg aspirin/day and were studied before the start of aspirin therapy, 24 hours after the first aspirin dose, and 4 and 24 hours after the day-14 aspirin dose.…”

Section: Subjects and Methods Drugsmentioning

confidence: 99%

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

et al. 1989

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ing men produced more thromboxane B2 (3.99±0.76 ng/ml) than nonsmoking women (2.13±0.24 ng/ml). Female smokers produced more thromboxane B2 (5.01±0.97 ng/ml) than nonsmoking women. Twenty-four hours after a single dose of 600 mg aspirin, in vitro production of thromboxane B2 in response to collagen fell by 95%, whereas in vivo production of thromboxane B2 and 6-keto-PGF,a in bleeding time blood fell by 87% and 66%, respectively. Subjects with the lowest absolute levels of thromboxane B2 24 hours after aspirin were also those with the longest postaspirin bleeding times. Recovery of 6-keto-PGFla production was faster than recovery of thromboxane B2 production, but 6-keto-PGFI, production for most subjects was still below basal 72 hours after aspirin. The influence of two different doses of long-term aspirin (80 mg every other day and 325 mg daily) on the in vivo production of thromboxane B2 and 6-keto-PGFl. was studied in normals and diabetics. After 14 days of 80 mg aspirin every other day, thromboxane B2 and 6-keto-PGFIa production were both substantially inhibited (93% and 78%, respectively). After 14 days of 325 mg aspirin daily, thromboxane B2 production was similarly substantially inhibited (93%), whereas 6-keto-PGFIa was significantly less affected (only 45% inhibition). Study of a second group of five normal subjects confirmed that 6-keto-PGFl. production was significantly inhibited 24 hours after the first dose of 325 mg aspirin but was not significantly less than basal after 14 days of 325 mg aspirin. The results suggest that 325 mg aspirin daily is more antithrombotic compared with 80 mg every other day due to the superior preservation of prostacyclin production. (Circulation 1989;79:29-38) T hromboxane A2, a potent vasoconstrictor and platelet-aggregating agent produced by platelets, and prostacyclin, a potent vasodilator and platelet inhibitor produced by vascular tissue, are believed to exert critical modulatory roles in vivo.1,2 Variations in the production of these comFrom the

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“…However, in vivo thrombus formation in the rat was found to be diminished after administration of acetylsalicylic acid (10 mg kg-) irrespective of pretreatment with sodium salicylate in different doses thus suggesting no effect of salicylate on the antithrombotic action of the acetylated compound (Philp & Paul, 1981). When acetylsalicylic acid was administered at doses between 20 and 1500 mg daily, thromboxane B2 (TXB2) formation in serum remained suppressed during a prolonged treatnment period up to 30 days (Patrignani et al, 1982;Viinikka et al, 1983;Weksler et al, 1983), and administration of sodium salicylate did not affect the inhibitory effect of acetylsalicylic acid on serum thromboxane formation and platelet aggregation (Dahl & Uotila, 1984;Nitelius etal., 1984). These studies make a clinically relevant interaction between these two drugs less likely.…”

Section: Introductionmentioning

confidence: 99%

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Rosenkranz¹,

Fischer²,

Meese³

et al. 1986

Brit J Clinical Pharma

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The present study was designed to investigate the effects of salicylate on the antiplatelet action of acetylsalicylic acid as well as on in vivo prostanoid formation and platelet function in healthy volunteers. In the first study six female volunteers received 350 mg acetylsalicylic acid intravenously, with and without previous oral administration of sodium salicylate (1200 mg daily for 3 days). Urinary prostanoid excretion as well as platelet aggregation and thromboxane formation were measured before and during salicylate and after acetylsalicylic acid. In the second study seven female volunteers received sodium salicylate (52.6 mg kg‐1) or acetylsalicylic acid (60.7 mg kg‐1) for 8 days in a randomized cross‐over protocol. Urinary prostanoid excretion, platelet aggregation and thromboxane formation as well as salicylate plasma concentrations were determined before, during and after administration of each drug. Sodium salicylate did not impair the complete suppression of arachidonic acid‐induced platelet thromboxane formation and aggregation obtained by the single intravenous dose of acetylsalicylic acid in the first study. Sodium salicylate in the second study did not affect urinary excretion of prostaglandin E2, its major urinary metabolite (7 alpha‐hydroxy‐5,11‐ diketo‐tetranor‐prostane‐1,16‐dioic acid), and 2,3‐dinor‐6‐keto‐ prostaglandin F1 alpha, the main urinary metabolite of epoprostenol (prostacyclin, PGI2). In contrast, acetylsalicylic acid significantly decreased excretion rates of these prostanoids by 64, 59 and 61%, respectively. In both studies platelet aggregation and thromboxane formation induced by collagen, thrombin or arachidonic acid were not significantly affected by salicylate administration, whereas acetylsalicylic acid inhibited platelet aggregation induced by all three agents as well as thrombin‐ and arachidonic acid induced thromboxane formation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

Cited by 116 publications

References 31 publications

Effects of a Thromboxane A2-Receptor Antagonist, a Thromboxane Synthetase Inhibitor and Aspirin on Prostaglandin I2 Production in Endothelium-Intact and -Injured Aorta of Guinea Pigs

Effects of a Thromboxane A2-Receptor Antagonist, a Thromboxane Synthetase Inhibitor and Aspirin on Prostaglandin I2 Production in Endothelium-Intact and -Injured Aorta of Guinea Pigs

In vivo measurement of thromboxane B2 and 6-keto-prostaglandin F1 alpha in humans in response to a standardized vascular injury and the influence of aspirin.

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

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