Synergistic effect of prostaglandin E1 and isosorbide dinitrate in peripheral vascular disease

Sinzinger, H.; Fitscha, P; O’Grady, John; Rauscha, F; Rogatti, W.; Vane, John R.

doi:10.1016/0140-6736(90)90412-x

Cited by 62 publications

(14 citation statements)

References 16 publications

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“…Furthermore, the same agents (vs 8-Br-cAMP) inhibit platelet adhesion at the sites of balloon catheter induced vascular injury in rats . These findings, in conjunction with others demonstrating definitive antiplatelet effects of cGMP-elevating agents in animals and humans (Fitzgerald 1987;Lam et al 1988;Eisert and Muller 1990;Sinzinger et al 1990;Aono et al 1991;Moncada et al 1991;Stamler and Loscalzo 1991;Geiger et al 1992;Chirkov et al 1993), clearly support the notion that cGMP is an effective mechanism in inhibiting platelet adhesion and aggregation. E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-carboxylate sesquihydrate), in comparison to dipyridamole and zaprinast (Beavo, 1995), is a highly selective and potent inhibitor of type V phosphodiesterase(PDE5) which is specific for cGMP, with a K i value of 2.4 nM against the isozyme from human aorta (Miyahara et al 1995;Saeki et al 1995;Polson and Strada, 1996).…”

Section: Introductionsupporting

confidence: 66%

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs

Chiu¹,

Vemulapalli²,

Chintala³

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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E4021 (sodium 1-[6-chloro-4-(3, 4-methylenedioxybenzyl)-aminoquinazolin-2-yl]piperidine-4-ca rboxylate sesquihydrate) is a highly selective and potent inhibitor of type V phosphodiesterase(PDE5). The in vitro and in vivo effect of E4021 on platelet function was evaluated, using echistatin, a potent disintegrin, as a positive reference agent. E4021 inhibits aggregatory response to collagen in washed human platelets (IC50 = 5 microM, vs. 0.14 microM with echistatin). In the ex vivo-platelet aggregation assay using whole blood from treated guinea pigs, E4021 (9 mg/kg i.v.) showed a moderate inhibition (43%) against collagen (0.125 microg/ml), whereas echistatin (250 microg/kg i.v.) exerted a 88% inhibition. The absence of endothelium-derived factors (NO) may account for the moderate in vitro and ex vivo antiplatelet activity of E4021. In an in vivo model of reversible platelet aggregation elicited by collagen (100 microg/kg i.v.), both E4021 and echistatin attenuated the intrapulmonary platelet accumulation in guinea pigs (-36% and -44%, respectively). In addition, E4021 (9 mg/kg i.v.) and echistatin (250 microg/kg i.v.) caused a similar inhibition of platelet adhesion at sites of microfilament-induced vascular injury in guinea pigs (52% and 65%, respectively). The two agents in combination did not show additive effect, suggesting that E4021 inhibits platelet activation and impairs interactions of adhesion receptors with matrix proteins. E4021 caused a selective increase in cGMP concentrations in the platelets isolated from treated guinea pigs: cAMP was not affected. It is concluded that the antiplatelet activity of E4021 is mediated through cGMP mechanism by virtue of selective inhibition of PDE5 in the platelets.

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Section: Introductionsupporting

confidence: 66%

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs

Chiu¹,

Vemulapalli²,

Chintala³

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In this context, platelet products released during aggregation in vivo may cause contraction of de-endothelialized canine coronary artery rings, whereas they induce relaxation in presence of endothelium [23]. Interestingly, isosorbide dinitrate, which releases NO, and prostaglandin E acted synergistically to reduce platelet deposition and to increase their survival time in patients with peripheral vascular disease [24]. …”

Section: Physiology Of Nitric Oxidementioning

confidence: 99%

Nitric Oxide as a Unique Bioactive Signaling Messenger in Physiology and Pathophysiology

Tuteja

Chandra

Tuteja

et al. 2004

BioMed Research International

196

128

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Nitric oxide (NO) is an intra- and extracellular messenger that mediates diverse signaling pathways in target cells and is known to play an important role in many physiological processes including neuronal signaling, immune response, inflammatory response, modulation of ion channels, phagocytic defense mechanism, penile erection, and cardiovascular homeostasis and its decompensation in atherogenesis. Recent studies have also revealed a role for NO as signaling molecule in plant, as it activates various defense genes and acts as developmental regulator. In plants, NO can also be produced by nitrate reductase. NO can operate through posttranslational modification of proteins (nitrosylation). NO is also a causative agent in various pathophysiological abnormalities. One of the very important systems, the cardiovascular system, is affected by NO production, as this bioactive molecule is involved in the regulation of cardiovascular motor tone, modulation of myocardial contractivity, control of cell proliferation, and inhibition of platelet activation, aggregation, and adhesion. The prime source of NO in the cardiovascular system is endothelial NO synthase, which is tightly regulated with respect to activity and localization. The inhibition of chronic NO synthesis leads to neurogenic and arterial hypertensions, which later contribute to development of myocardial fibrosis. Overall, the modulation of NO synthesis is associated with hypertension. This review briefly describes the physiology of NO, its synthesis, catabolism, and targeting, the mechanism of NO action, and the pharmacological role of NO with special reference to its essential role in hypertension.

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“…1990 a) or in vivo (Knowles, Salter, Brooks & Moncada, 1990). Induction can also be effected by cytokines including interleukin-1 (IL-1), tumour necrosis factor (TNF) and gamma interferon ( (Sneddon & Vane, 1988) and may synergize with prostacyclin and PGE1 in this action (Radomski et al 1987b;Sinzinger, Fitscha, O'Grady, Rauscha, Rogatti & Vane, 1990). However, the physiological effects of endogenous endothelium-derived NO on platelet and white cell function in vivo are not yet clear.…”

Section: Smooth Musclementioning

confidence: 99%

Nitric oxide and cardiovascular control

Calver¹,

Collier²,

Vallance³

1993

Experimental Physiology

167

113

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Synergistic effect of prostaglandin E1 and isosorbide dinitrate in peripheral vascular disease

Cited by 62 publications

References 16 publications

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs

Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs

Nitric Oxide as a Unique Bioactive Signaling Messenger in Physiology and Pathophysiology

Nitric oxide and cardiovascular control

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