Different Effects of a Thromboxane Mimetic on Blood Flow and Plasma Exudation in Guinea Pig Airways and Skeletal Muscle

Cui, ZH; Okazawa, Akira; Skoogh, Bengt-Eric; Lötvall, Jan

doi:10.1016/s0090-6980(97)89600-1

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…Although L ‐NAME enhanced eicosanoid‐dependent ET B receptor‐mediated effects of intravenously injected ET‐1 in both the pulmonary and cardiovascular systems, the particular eicosanoids involved in increasing PIP and reducing MAP in this condition are suggested to be distinct. As already discussed, the main eicosanoid mobilized by ET‐1 in the lung is likely to be TxA 2 , but this potent vasoconstrictor ( Hamberg et al ., 1975 ) elevates MAP in the guinea‐pig, as evidenced by our results with the TxA 2 ‐mimetic U 46619 and those of Cui et al . (1997) .…”

Section: Discussionsupporting

confidence: 87%

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Lewis

Cadieux

Rae

et al. 1999

British J Pharmacology

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1 This study attempts to investigate if endogenous nitric oxide (NO) can modulate the eicosanoidreleasing properties of intravenously administered endothelin-1 (ET-1) in the pulmonary and circulatory systems in the guinea-pig. 2 The nitric oxide synthase blocker N o -nitro-L-arginine methyl ester (L-NAME; 300 mM; 30 min infusion) potentiated, in an L-arginine sensitive fashion, the release of thromboxane A 2 (TxA 2 ) stimulated by ET-1, the selective ET B receptor agonist IRL 1620 (Suc-[Glu 9 ,Ala 11,15 ]-ET-1(8-21)) or bradykinin (BK) (5, 50 and 50 nM, respectively, 3 min infusion) in guinea-pig isolated and perfused lungs. 3 In anaesthetized and ventilated guinea-pigs intravenous injection of ET-1 (0.1 ± 1.0 nmol kg 71 ), IRL 1620 (0.2 ± 1.6 nmol kg 71 ), BK (1.0 ± 10.0 nmol kg 71 ) or U 46619 (0.2 ± 5.7 nmol kg 71 ) each induced dose-dependent increases in pulmonary insu ation pressure (PIP). Pretreatment with L-NAME (5 mg kg 71 ) did not change basal PIP, but increased, in L-arginine sensitive manner, the magnitude of the PIP increases (in both amplitude and duration) triggered by each of the peptides (at 0.25, 0.4 and 1.0 nmol kg 71 , respectively), without modifying bronchoconstriction caused by U 46619 (0.57 nmol kg 71 ). 4 The increases in PIP induced by ET-1, IRL 1620 (0.25 and 0.4 nmol kg 71 , respectively) or U 46619 (0.57 nmol kg 71 ) were accompanied by rapid and transient increases of mean arterial blood pressure (MAP). Pretreatment with L-NAME (5 mg kg 71 ; i.v. raised basal MAP persistently and, under this condition, subsequent administration of ET-1 or IRL 1620, but not of U-46619, induced hypotensive responses which were prevented by pretreatment with the cyclo-oxygenase inhibitor indomethacin. 5 Thus, endogenous NO appears to modulate ET-1-induced bronchoconstriction and pressor e ects in the guinea-pig by limiting the peptide's ability to induce, possibly via ET B receptors, the release of TxA 2 in the lungs and of vasodilatory prostanoids in the systemic circulation. Furthermore, it would seem that these eicosanoid-dependent actions of ET-1 in the pulmonary system and on systemic arterial resistance in this species are physiologically dissociated.

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Section: Discussionsupporting

confidence: 87%

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Lewis

Cadieux

Rae

et al. 1999

British J Pharmacology

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“…In guinea‐pig models, a Tx 2 mimetic compound, U‐46619, has been shown to cause plasma exudation in nasal mucosa and consistently increase intranasal pressure (Yasui et al , 1997; Yamasaki et al , 1997). Cui et al (1997) have demonstrated that plasma exudation in guinea‐pig airway induced by systemic administration of U‐46619 is associated with the increased local blood flow which is caused by the increased inflow pressure in the aorta due to its potent vasoconstrictor activity, but not by vasodilatation. Thus, TxA 2 ‐mediated plasma exudation in guinea‐pig nasal mucosa may occur via the same mechanism as observed in airway.…”

Section: Discussionmentioning

confidence: 99%

Characterization and localization of thromboxane A₂ receptor in human and guinea‐pig nasal mucosa using radiolabelled (+)‐S‐145

Arimura

Miwa

Hasegawa

et al. 1998

British J Pharmacology

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TxA2 receptor (TP‐receptor) antagonists such as S‐1452 and Bay u 3405 have been shown to be effective in alleviating nasal blockage in patients with allergic rhinitis as well as guinea‐pig allergic rhinitis models. The present study was conducted to examine the existence and localization of the TP‐receptor in human and guinea‐pig nasal mucosa by in vitro receptor binding autoradiography using radiolabelled (+)‐S‐145, which is a potent and specific TP‐receptor antagonist with an extremely slow dissociation rate. We ascertained the binding specificity of [3H]‐(+)‐S‐145 in human and guinea‐pig platelet membranes by comparing the ability of four TP‐receptor ligands of U‐46619, (+)‐S‐145, I‐(+)‐S‐145 and Bay u 3405 to displace the specific binding of [3H]‐(+)‐S‐145 and [3H]‐U‐46619. The rank order of potency (Ki) for the displacement was correlated highly with that determined from [3H]‐U‐46619 binding to the same preparations. Quantitative autoradiography using a radioluminographic imaging plate system, in which the radioactivity of [3H]‐(+)‐S‐145 is expressed as photostimulated luminescence (PSL) per area (mm2), revealed that specific binding of [3H]‐(+)‐S‐145 to human and guinea‐pig nasal mucosa was saturable. Scatchard analysis showed about three fold higher affinity and two fold greater maximal binding to the nasal mucosa of humans than that of guinea‐pigs: the KD and Bmax values in human mucosa were 2.82±0.35 nM and 6.47±0.33 PSL mm−2 and those in guinea‐pig mucosa were 8.23±1.93 nM and 3.37±0.66 PSL mm−2, respectively. Specific [3H]‐(+)‐S‐145 binding to cryostat sections of human and guinea‐pig nasal mucosa was displaced by another TP‐receptor antagonist, Bay u 3405, and a TP‐receptor agonist, U‐46619. The order of potency (Ki value: nM) was (+)‐S‐145 (2.5) > Bay u 3405 (15.4) >> U‐46619 (359.6) in human nasal mucosa and (+)‐S‐145 (22.8) > U‐46619 (49.8) & Bay u 3405 (62.1) in guinea‐pig nasal mucosa. These rank orders showed rather good correlation with those obtained for the respective platelet membranes. Autoradiographs of human nasal mucosa demonstrated that specific [125I]‐(+)‐S‐145 binding sites mainly exist on the smooth muscle layers of venous sinusoids and arterioles in the lamina propria, with few or no binding sites in the epithelium and nasal gland. We concluded that radiolabelled (+)‐S‐145 can be used as a TP‐receptor ligand for autoradiographic study, and that the TP‐receptor is exclusively located on smooth muscle layers of venous sinusoids and arterioles in the nasal mucosa. The potent vasoconstrictive activity of TxA2 may cause reduction of local blood flow followed by mucosal oedema probably through mechanisms of vascular injury such as ischaemia‐reperfusion.

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Different Effects of a Thromboxane Mimetic on Blood Flow and Plasma Exudation in Guinea Pig Airways and Skeletal Muscle

Cited by 2 publications

References 24 publications

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Characterization and localization of thromboxane A₂ receptor in human and guinea‐pig nasal mucosa using radiolabelled (+)‐S‐145

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Different Effects of a Thromboxane Mimetic on Blood Flow and Plasma Exudation in Guinea Pig Airways and Skeletal Muscle

Cited by 2 publications

References 24 publications

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Nitric oxide limits the eicosanoid‐dependent bronchoconstriction and hypotension induced by endothelin‐1 in the guinea‐pig

Characterization and localization of thromboxane A2 receptor in human and guinea‐pig nasal mucosa using radiolabelled (+)‐S‐145

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Characterization and localization of thromboxane A₂ receptor in human and guinea‐pig nasal mucosa using radiolabelled (+)‐S‐145