Prostaglandin control of plasma and platelet 5-hydroxytryptamine in normal and embolized animals

Utsunomiya, Takayoshi; Krausz, M. M.; Shepro, David; Hechtman, Herbert B.

doi:10.1152/ajpheart.1981.241.5.h766

Cited by 16 publications

(11 citation statements)

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“…Serotonin is important. Administration of the antagonist cyproheptadine before embolization, using the same preparation as reported in this study prevented any rise in PVR (20).…”

Section: Introductionmentioning

confidence: 53%

“…A selective PGI2 effect of vaso-and bronchodilation has been suggested by our finding that a PGE1 infusion will reduce MPAP to levels lower than PGI2, but surprisingly, will worsen Qs/QT and VD/VT (18). Other actions of PGI2 are to antagonize the vaso-and broncho-constriction induced by 5-HT infusion (19) and to lower plasma 5-HT levels after experimental pulmonary embolization (20). Since PGI2 modifies plasma and platelet 5-HT transport, it is possible that PGI2 not only acts directly to relax vascular and bronchial smooth muscle, but also acts indirectly in inhibiting the synthesis and/or release of the platelet agents, TxA2 and 5-HT, which mediate smooth muscle constriction.…”

Section: Introductionmentioning

confidence: 99%

“…An infusion of 5-HT will lower arterial oxygen tension that can be restored by a simultaneous infusion of PGI2 (19). In this setting, PGI2 may be acting both as a bronchodilator as well as a promotor of rapid 5-HT clearance by platelets (20). Pretreatment with imidazole and indomethacin inhibits TxA2 synthesis (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Utsunomiya¹,

Krausz²,

Levine³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg -h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI2) 100 qg/kg. min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF,a, the stable hydrolysis product of PGI2, from 0.11±0.08 ng/ml (mean±SD) to 0.33±0.10 7g/ml (P < 0.005) and TxB2, the stable product of TxA2, from 0.10±0.04 qg/ml to 0.38±0.0611g/ml (P < 0.001). Increases were observed in total dead space (VD/VT) from 0.46±0.03 to 0.61±0.08 (P < 0.025, physiologic shunting (Qs/(T) from 16±4% to 38±9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27±0.59 mm Hg.min/liter to 9.21±1.90 mm Hg* min/liter (P < 0.005) and mean pulmonary arterial pressure from 14±6 mm Hg to 34±1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139±11 ml/kg.min to 95±17 ml/kg.min in 4h (P < 0.025). Imidazole pretreatment prevented a rise of TxB2, but not 6-keto-PGFj,; indomethacin blocked both. Both agents maintained VD/VT at base line and limited increases in Qs/QT and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). < 0.025), QS/QT (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI2 infusion, CI was higher than controls. Concentrations of TxB2 correlated with VD/VT, r = 0.79 and Qs/QT, r = 0.69 (P < 0.001).Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that VD/VT is closely allied to TxA2 levels.

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“…Serotonin is important. Administration of the antagonist cyproheptadine before embolization, using the same preparation as reported in this study prevented any rise in PVR (20).…”

Section: Introductionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Utsunomiya¹,

Krausz²,

Levine³

et al. 1982

J. Clin. Invest.

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“…In addition, flushing in the carcinoid syndrome is inhibited by an antiserotonergic agent (Loong et al, 1968) and by cyproheptadine (Plank and Feldman, 1975). Interestingly, one paper reported that prostaglandins may control plasma serotonin levels (Utsunomiya et al, 1981), whereas another reported that subthreshold serotonin concentrations potentiated the effect of low arachidonic acid on human platelet aggregation (Saeed et al, 2003). The possibility still remains that serotonin may be inducing PGD 2 release or vice versa.…”

Section: Discussionmentioning

confidence: 99%

Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Papaliodis

Boucher²,

Kempuraj³

et al. 2008

J Pharmacol Exp Ther

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Niacin lowers serum cholesterol, low-density lipoprotein, and triglycerides, and it raises high-density lipoprotein. However, most patients experience cutaneous warmth and vasodilation (flush). Acetylsalicylic acid (ASA) can reduce this flush, presumably by decreasing prostaglandin D 2 (PGD 2 ) release from macrophages. Here, we show that methylnicotinate induces significant PGD 2 release from human mast cells and serotonin from human platelets. Intradermal injection of methylnicotinate induces rat skin vasodilation and vascular permeability. Niacin increases plasma PGD 2 and serotonin in a rat model of flush. The phenothiazine prochlorperazine, the H 1 , serotonin receptor antagonist cyproheptadine, and the specific serotonin receptor-2A antagonist ketanserin inhibit niacin-induced temperature increase by 90% (n ϭ 5, p Ͻ 0.05), 90 and 50% (n ϭ 3, p Ͻ 0.05), and 85% (n ϭ 6, p ϭ 0.0008), respectively, in this animal model. These results indicate that niacin-induced flush involves both PGD 2 and serotonin, suggesting that drugs other than ASA are required to effectively inhibit niacin-induced flush.

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“…Although the plasma concentrations of free serotonin are low (40,164), they obviously augment dramatically during platelet aggregation, as illustrated in embolized animals (245). The monoamine can be taken up by the adrenergic nerves in the blood vessel wall and subsequently released (138,282).…”

Section: In Vivomentioning

confidence: 99%

Ketanserin

Nueten

Janßen

Symoens

et al. 1987

Cardiovascular Drug Reviews

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Prostaglandin control of plasma and platelet 5-hydroxytryptamine in normal and embolized animals

Cited by 16 publications

References 0 publications

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Ketanserin

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Prostaglandin control of plasma and platelet 5-hydroxytryptamine in normal and embolized animals

Cited by 16 publications

References 0 publications

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Niacin-induced “Flush” Involves Release of Prostaglandin D2from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Ketanserin

Contact Info

Product

Resources

About

Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model