Dipyridamole: A possible potent inhibitor of thromboxane A2 synthetase in vascular smooth muscle

Ai, Ally; Ms, Manku; Df, Horrobin; Morgan, Reginald O.; M, Karmazin; Ra, Karmali

doi:10.1016/0090-6980(77)90278-7

Cited by 54 publications

(8 citation statements)

References 8 publications

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“…A marked and longer-lasting vasoconstriction induced by AA led to a diminished left ventricular systolic pressure most probably secondary to the relative hypoxia resulting from the diminished coronary flow. Dpy, which has been shown to inhibit the formation of TxA2 without inhibiting the synthesis of other PGL (Ally, Manku, Horrobin, Morgan, Karmazyn & Karmali, 1977;Greenwald, Wong, Rao, Bianchine & Panganamala, 1978) would prevent AA-induced coronary constriction in our experiments. TxA2 formation is also inactivated by ASA as was shown by the cyclo-oxygenase acetylation in platelets (Burch, Stanford & Majerus, 1978).…”

Section: Discussionmentioning

confidence: 55%

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

Belo

Talesnik

1982

British J Pharmacology

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1 The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator.2 The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5mg/l) and naproxen (12.5-25 mg/I) reversibly inhibited both phases of the response induced by AA. 3 Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. 4 Short infusions of acetylsalicylic acid at low concentrations (2.9 Lg/ml), dipyridamole (0.6 pg/ml) and sulphinpyrazone (28.7 pg/ml) selectively inhibited the vasoconstrictor phase of the response to AA. 5 It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. 6 Linolenic, linoleic, dihomo-y-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. 7 Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. 8 The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. 9 Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.

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Section: Discussionmentioning

confidence: 55%

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

Belo

Talesnik

1982

British J Pharmacology

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“…Benzydamine [69] and imidazole [70,71] are partially selective inhibitors of throm boxane synthetase, a property claimed [72] but also negated [66] for dipyridamole (ta ble III). Selectivity of these agents is however to be regarded as both relative and tenta tive.…”

Section: Compounds Inhibiting the Formation Of Thromboxane A2mentioning

confidence: 99%

A Pharmacological Approach to the Inhibition of Platelet Adhesion and Platelet Aggregation

Verstraete¹

1982

Pathophysiol Haemos Thromb

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A first level of pharmacological interference with platelet function is located at the site of the agonist-receptor interaction (receptors for collagen, adenosine diphosphate, serotonin, fibrinogen). A second level of interaction is to prevent the mobilization of intra-cellular calcium ions which can be obtained by inhibition of phosphodiesterase, activation of cAMP (e.g. with prostacyclin analogues), inhibition of thromboxane A₂ formation or blocking of its receptors. Compounds preventing the platelet contractile process or platelet secretion could theoretically also prevent some platelet functions.

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“…DIP attenuates platelet aggregability through several mechanisms. DIP inihibits thromboxane synthase, limiting the conversion of prostaglandin to thromboxane, an inducer of platelet aggregation and vasoconstrictor [22,23]. Also, by limiting adenosine uptake into platelets, DIP initiates the buildup of intraplatelet cyclic adenosine monophosphate, blocking the platelet response to ADP [15].…”

Section: Discussionmentioning

confidence: 99%

Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral Circulation and Outcome in Rabbits

d’Esterre

Tichauer

Aviv

et al. 2011

Transl. Stroke Res.

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Clinical observations have indicated that secondary treatment with dipyridamole (DIP) may ameliorate stroke severity. The purpose of this study was to explore the effect of pre-stroke DIP treatment on stroke outcome in a rabbit model of embolic occlusion. Twenty male New Zealand white rabbits were randomly selected for intravenous treatment with DIP (n = 10) or saline (n = 10) for 7 days prior to an embolic cerebral occlusion by an autologous blood clot. Multiple computed tomography perfusion scans were acquired out to 28 days post-stroke to map cerebrohemodynamics, in conjunction with neurological assessments and histopathology. The DIP-treated group fared better than the saline group on several accounts: 66% of them survived to 28 days, whilst saline animals all had to be euthanized by day 7 due to severe neurological deficits. They presented with significantly more viable tissue in the ischemic hemisphere as well as fewer neurological deficits on days 4 and 7. Furthermore, DIP-treated animals exhibited improved cerebrohemodynamics by 24 h and had less incidence of haemorrhage within their infarcted regions (p < 0.05). DIP treatment prior to stroke onset can significantly improve neurological outcome, cerebral hemodynamics, and final infarct volume.

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Dipyridamole: A possible potent inhibitor of thromboxane A2 synthetase in vascular smooth muscle

Cited by 54 publications

References 8 publications

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

A Pharmacological Approach to the Inhibition of Platelet Adhesion and Platelet Aggregation

Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral Circulation and Outcome in Rabbits

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