Thromboxane A2: Effects of airway and vascular smooth muscle

Svensson, Jan; Strandberg, Kjell; Tuvemo, Torsten; Hámberg, Mats

doi:10.1016/0090-6980(77)90258-1

Cited by 245 publications

(51 citation statements)

References 17 publications

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“…From our data, we cannot determine whether the effects of PGH2 are a direct result of its action on the smooth muscle of the resistance vessels of the lung, or whether conversion to its metabolite thromboxane A2 is necessary first. Thromboxane A2 is more potent than PGH2 in contracting large arterial smooth muscle and in inducing aggregation ofplatelets in vitro (22,23). Because it is formed from PGH2 in the lung (24), it is possible that the hemodynamic effects of PGH2 are mediated through this more active metabolite.…”

Section: Statisticsmentioning

confidence: 99%

Effects of Prostaglandin Cyclic Endoperoxides on the Lung Circulation of Unanesthetized Sheep

Bowers¹,

Ellis²,

Brigham³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Although prostaglandins E2 and F2, have been suggested as mediators of the pulmonary hypertension seen after endotoxin infusion or during alveolar hypoxia, their precursors, the endoperoxides (prostaglandins G2 and H2) are much more potent vasoconstrictors in vitro. In this study we compared the effects of prostaglandin (PG)H2, a stable 9-methylene ether analogue of PGH2 (PGH2-A), PGE2, and PGF2a on pulmonary hemodynamics in awake sheep. The animals were prepared to allow for measurement of (a) INTRODUCTIONThe agents mediating the pulmonary hypertension seen with alveolar hypoxia and gram-negative endotoxin infusion have not been identified. Because prostaglandins (PG)l E2 and F2, are released from the lungs during these reactions, they have been implicated as the mediators, but neither is an impressive vasoconstrictor in vitro (1, 2). In contrast, their precursors, the endoperoxides PGG2 and PGH2, are powerful vasoconstrictors, -100 times more potent in constricting isolated smooth muscle (3).Because the endoperoxides are unstable and difficult to synthesize in the large amounts needed for in vivo studies, we first used a stable 9-methylene ether analogue of PGH2 (PGH2-A; [15S] hydroxy-lla, 9a-[epoxymethano] prosta-5Z, 13E-dienoic acid, [4]) to assess the effects of endoperoxides on pulmonary vascular pressures, permeability of the lung microcirculation, and lung fluid balance in awake sheep. We then prepared PGH2, itself, in amounts large enough for brief steady-state infusions, and compared its effects to those of the analogue, PGE2 and PGF2a,.

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Section: Statisticsmentioning

confidence: 99%

Effects of Prostaglandin Cyclic Endoperoxides on the Lung Circulation of Unanesthetized Sheep

Bowers¹,

Ellis²,

Brigham³

et al. 1979

J. Clin. Invest.

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“…It is known that TxA 2 can elicit bronchoconstriction by at least two mechanisms: 1) by potentiating the cholinergic neuroeffector transmission [11][12][13][14]; and 2) by direct stimulation of the TP prostanoid receptor on the airway smooth muscle, a cholinergic-independent mechanism [8][9][10]. The lack of additive effect of OKY-046 and atropine strongly suggests the contribution of a cholinergic-dependent mechanism in the TxA 2 action in the present model.…”

Section: Discussionmentioning

confidence: 52%

“…TxA 2 is known to contract the airway smooth muscle directly by stimulating the specific thromboxane (TP) prostanoid receptor on the muscle [8][9][10], or indirectly by potentiating the neuroeffector transmission of cholinergic contraction [11][12][13][14]. In addition, TxA 2 can produce plasma extravasation in the airways [15,16].…”

mentioning

confidence: 99%

Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs

et al. 1996

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“…We have reported previously that ET-1 induces release of TXA2 from the guinea-pig trachea in vitro, which may, in part, mediate its airway constrictor action in the guinea-pig (Filep et al, 1990;. Since TXA2 is a very potent constrictor in the guinea-pig airways (Svensson et al, 1977), one may expect that TXA2 receptor blockade would lead to potentiation of ET-1-induced relaxations.…”

Section: Discussionmentioning

confidence: 98%

Induction by endothelin‐1 of epithelium‐dependent relaxation of guinea‐pig trachea in vitro: role for nitric oxide

Filep

Battistini

Sirois

1993

British J Pharmacology

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The purpose of the present experiments was to study the underlying mechanisms responsible for the relaxant action of endothelin‐1 (ET‐1) in the guinea‐pig trachea in vitro. In tracheal strips precontracted (60–70% of the maximum) with carbachol, ET‐1 (1–100 nm) evoked slowly developing concentration‐dependent relaxations. Preincubation of the tissues with the thromboxane A2/prostaglandin H2 receptor antagonist, BM 13505 (5 μm) significantly potentiated the relaxant response to ET‐1. Removal of the epithelium changed the response of precontracted tracheal preparations to ET‐1 from a relaxation to a sustained contraction. ET‐1‐induced relaxations were abolished by methylene blue (10 μm) and were almost completely attenuated by oxyhaemoglobin (5 μm) and NG‐monomethyl‐l‐arginine (l‐NMMA, 100 μm), an inhibitor of nitric oxide synthesis, but were not altered by indomethacin (10 μm). In tracheal strips under passive tension, ET‐1 (1–100 nm) elicited dose‐dependent contractions. The sensitivity of tissues to ET‐1 was significantly enhanced by removal of the epithelium (apparent EC50 values were 28.1 ± 4.1 and 12.5 ± 0.8 nm in intact and rubbed trachea, respectively, n = 7, P < 0.01). Preincubation of intact tracheal strips with methylene blue, oxyhaemoglobin or l‐NMMA did not mimic the effect of epithelium removal on ET‐1‐induced contractions. There was a concentration‐dependent increase in thromboxane A2 but not in PGE2 and prostacyclin release from intact tracheal strips following stimulation with ET‐1 (5–100 nm). These results show that ET‐1 exerts a dual action on guinea‐pig isolated trachea: it evokes contractions at low resting tone, whereas it induces relaxations at higher resting tone. The relaxant action of ET‐1 may be mediated by nitric oxide released from epithelial cells and resultant activation of smooth muscle guanylate cyclase.

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Thromboxane A2: Effects of airway and vascular smooth muscle

Cited by 245 publications

References 17 publications

Effects of Prostaglandin Cyclic Endoperoxides on the Lung Circulation of Unanesthetized Sheep

Effects of Prostaglandin Cyclic Endoperoxides on the Lung Circulation of Unanesthetized Sheep

Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs

Induction by endothelin‐1 of epithelium‐dependent relaxation of guinea‐pig trachea in vitro: role for nitric oxide

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