Dipyridamole and vascular prostacyclin production

Boeynaems, Jean‐Marie; Coevordem, A. Van; Demolle, Dominique

doi:10.1016/0006-2952(86)90483-1

Cited by 17 publications

(7 citation statements)

References 33 publications

(37 reference statements)

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“…This is supported by our observation that cAMP elevation, by inhibiting phosphodiesterase activity with dipyridamole, did not influence eicosanoid synthesis (data not shown). This observation is in accordance with Boeynaems et al, 26 who observed that dipyridamole did not influence the ADP-induced biosynthesis of PGI 2 in aortic rings.…”

Section: +supporting

confidence: 82%

Functional implications of cAMP and Ca2+ on prostaglandin I2 and thromboxane A2 synthesis by human endothelial cells.

Griesmacher

Weigel

David

et al. 1992

Arterioscler Thromb

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Human umbilical vein endothelial cells were incubated with ATP, ADP, thrombin, or ionophore A23187 for as long as 600 seconds. A statistically significant rise in the prostaglandin I2 (prostacyclin; PGI2) and thromboxane A2 (TxA2) release was observed after 45 seconds. The maximum amount of cytosolic free Ca2+ was reached between 20 and 30 seconds. A statistically significant elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels was observed only in response to ATP and ADP after 120 seconds. Furthermore, adenosine, caffeine, phorbol 12-myristate 13-acetate (PMA), and adenosine 5'-(alpha, beta-methylene)triphosphate were tested alone or in combination with ATP or thrombin. PMA inhibited ATP-stimulated eicosanoid biosynthesis but had no effect on thrombin. Of the agents used to increase cytosolic free Ca2+ concentrations, only PMA failed to provoke eicosanoid release. Similarly, only PMA failed to induce a Ca2+ flux in the absence of extracellular Ca2+. The data presented show that PGI2 and TxA2 release from human umbilical cord endothelial cells is closely associated with Ca2+ mobilized from intracellular sources. Extracellular Ca2+, as well as changes in intracellular cAMP levels, has no influence on endothelial eicosanoid synthesis, at least for short-term regulation (less than or equal to 600 seconds).

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Section: +supporting

confidence: 82%

Functional implications of cAMP and Ca2+ on prostaglandin I2 and thromboxane A2 synthesis by human endothelial cells.

Griesmacher

Weigel

David

et al. 1992

Arterioscler Thromb

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“…It inhibits the active uptake of adenosine into cells at low concentration (10-6 M), whereas higher concentrations are required for cyclic AMP phos phodiesterase and adenosine deaminase inhibition (Phillis and Wu, 1982). In addition, no effect on prostacyclin concentrations occur at a concentra tion of 10-6 M (Boeynaems et al, 1986). In this study, we used CSF concentrations of dipyridamole (10-6 M) and theophylline (5 x 10-5 M), which presumably affect primarily adenosine availability and metabolism.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Dipyridamole and Theophylline on Rat Pial Vessels during Hypocarbia

Ibayashi

Ngai

Meno

et al. 1988

J Cereb Blood Flow Metab

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Hypocarbia results in an increase in brain adenosine concentrations, presumably because of brain hypoxia associated with hypocarbic vasoconstriction. It was hypothesized that adenosine limits the degree of hypocarbic vasoconstriction. To test this hypothesis, the effects of dipyridamole and theophylline on CO2 reactivity during hypocarbia were investigated in anesthetized rats. Dipyridamole should reduce the vasoconstriction by potentiating adenosine action, whereas theophylline should increase the vasoconstriction by blocking adenosine receptors. Cortical pial arterioles of mechanically ventilated and anesthetized rats were displayed on a video monitor system through a closed cranial window. Arterial blood pressure and oxygen tension were stable. CO2 reactivity, formulated as 100 X [delta diameter (micron)/resting diameter (micron)]/delta PaCO2 (mmHg), in the hypocarbic phase was calculated before and after topical superfusion of dipyridamole (10(-6) M; n = 7) and theophylline (5 X 10(-5) M; n = 6). CO2 reactivity was significantly decreased after superfusion of dipyridamole (0.57 +/- 0.08; mean +/- SEM) as compared with mock cerebrospinal fluid (CSF) (0.97 +/- 0.17, p less than 0.05, n = 7). On the other hand, CO2 reactivity after superfusion of theophylline was increased (1.63 +/- 0.28) as compared with mock CSF (1.00 +/- 0.20, p less than 0.05, n = 6), indicating that adenosine is involved in hypocarbic vasoconstriction.

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“…12 Increasing concentrations of cAMP affect platelet-activating factor, collagen, and adenosine diphosphate to inhibit platelet aggregation. 12, 16,17 Dipyridamole also inhibits platelet cyclic-3′,5′-guanosine monophosphate (cGMP) phosphodiesterase, which, in turn, inhibits platelet activation and aggregation. 12 Dipyridamole also stimulates prostacyclin synthesis and potentiates the antiplatelet effects of prostacyclin.…”

Section: Pharmacologymentioning

confidence: 99%

Aggrenox: A Fixed-Dose Combination of Aspirin and Dipyridamole

Lenz

Hilleman

2000

Ann Pharmacother

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The American College of Chest Physicians (ACCP) recommends aspirin 50-325 mg/d to be the initial antiplatelet of choice for the prevention of atherothrombotic cerebral ischemic events. However, with the favorable results of the ESPS-2, it may be appropriate to substitute aspirin/ER dipyridamole for aspirin alone as the drug of choice. This combination appears to have a favorable adverse effect profile. The relative effectiveness of aspirin/ER dipyridamole compared with clopidogrel and ticlopidine has yet to be determined. If alternative antiplatelet therapy is needed, the ACCP recommends clopidogrel rather than ticlopidine because of its lower incidence of adverse effects. The ACCP further states that the combination of aspirin plus dipyridamole may be more effective than clopidogrel; these agents have a similarly favorable adverse effect profile.

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Dipyridamole and vascular prostacyclin production

Cited by 17 publications

References 33 publications

Functional implications of cAMP and Ca2+ on prostaglandin I2 and thromboxane A2 synthesis by human endothelial cells.

Functional implications of cAMP and Ca2+ on prostaglandin I2 and thromboxane A2 synthesis by human endothelial cells.

The Effects of Dipyridamole and Theophylline on Rat Pial Vessels during Hypocarbia

Aggrenox: A Fixed-Dose Combination of Aspirin and Dipyridamole

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