The Experts below are selected from a list of 12 Experts worldwide ranked by ideXlab platform
Jean-pierre Valentin - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the pulmonary hypertensive effects of the Isoprostane Derivative, 8-iso-PGF2α, in the rat
British journal of pharmacology, 1997Co-Authors: Gareth W. John, Jean-pierre ValentinAbstract:1 We analysed the pulmonary hypertensive effects of the F2-Isoprostane Derivative, 8-iso-prostaglandin F2α (8-iso-PGF2α), in comparison with those of the high efficacy thromboxane A2/prostanoid (TP) receptor agonist, U-46619, in pentobarbitone-anaesthetized, open-chest rats (n=4–15 per group). 2 8-iso-PGF2α produced dose-dependent increases in mean pulmonary arterial pressure, with an ED50 of 39.0 (31.4–50.6) μg kg−1, i.v. (geometric mean with 95% confidence limits in parentheses) compared to 1.4 (1.1–2.3) μg kg−1, i.v., for U-46619. The maximum responses evoked by U-46619 and 8-iso-PGF2α were not statistically significantly different (21.0±1.0 and 25.8±1.9 mmHg at 10 μg kg−1 of U-46619 and 630 μg kg−1 of 8-iso-PGF2α, respectively). 3 The TP receptor antagonist, SQ 29,548 (0.63 mg kg−1, i.v. + 0.63 mg kg−1 h−1) fully antagonised both U-46619 and 8-iso-PGF2α-induced pulmonary hypertensive responses. 4 Further experiments were carried out to determine whether 8-iso-PGF2α antagonized the pulmonary hypertensive responses evoked by U-46619, or those induced by itself, as would be predicted for a partial agonist. However, ED10 or ED25 doses of 8-iso-PGF2α (10 or 20 μg kg−1, i.v.) failed to reduce the pulmonary hypertensive responses induced either by U-46619 or by itself. 5 The data suggest that in the pulmonary vascular bed of the rat, 8-iso-PGF2α acts as an agonist of high intrinsic activity at SQ 29,548-sensitive (probably TP) receptors. British Journal of Pharmacology (1997) 122, 899–905; doi:10.1038/sj.bjp.0701441
Gareth W. John - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the pulmonary hypertensive effects of the Isoprostane Derivative, 8-iso-PGF2α, in the rat
British journal of pharmacology, 1997Co-Authors: Gareth W. John, Jean-pierre ValentinAbstract:1 We analysed the pulmonary hypertensive effects of the F2-Isoprostane Derivative, 8-iso-prostaglandin F2α (8-iso-PGF2α), in comparison with those of the high efficacy thromboxane A2/prostanoid (TP) receptor agonist, U-46619, in pentobarbitone-anaesthetized, open-chest rats (n=4–15 per group). 2 8-iso-PGF2α produced dose-dependent increases in mean pulmonary arterial pressure, with an ED50 of 39.0 (31.4–50.6) μg kg−1, i.v. (geometric mean with 95% confidence limits in parentheses) compared to 1.4 (1.1–2.3) μg kg−1, i.v., for U-46619. The maximum responses evoked by U-46619 and 8-iso-PGF2α were not statistically significantly different (21.0±1.0 and 25.8±1.9 mmHg at 10 μg kg−1 of U-46619 and 630 μg kg−1 of 8-iso-PGF2α, respectively). 3 The TP receptor antagonist, SQ 29,548 (0.63 mg kg−1, i.v. + 0.63 mg kg−1 h−1) fully antagonised both U-46619 and 8-iso-PGF2α-induced pulmonary hypertensive responses. 4 Further experiments were carried out to determine whether 8-iso-PGF2α antagonized the pulmonary hypertensive responses evoked by U-46619, or those induced by itself, as would be predicted for a partial agonist. However, ED10 or ED25 doses of 8-iso-PGF2α (10 or 20 μg kg−1, i.v.) failed to reduce the pulmonary hypertensive responses induced either by U-46619 or by itself. 5 The data suggest that in the pulmonary vascular bed of the rat, 8-iso-PGF2α acts as an agonist of high intrinsic activity at SQ 29,548-sensitive (probably TP) receptors. British Journal of Pharmacology (1997) 122, 899–905; doi:10.1038/sj.bjp.0701441
Valentin Jean-pierre - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the pulmonary hypertensive effects of the Isoprostane Derivative, 8-iso-PGF(2α), in the rat
1997Co-Authors: John, Gareth W, Valentin Jean-pierreAbstract:1. We analysed the pulmonary hypertensive effects of the F(2)-Isoprostane Derivative, 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), in comparison with those of the high efficacy thromboxane A(2)/prostanoid (TP) receptor agonist, U-46619, in pentobarbitone-anaesthetized, open-chest rats (n=4–15 per group). 2. 8-iso-PGF(2α) produced dose-dependent increases in mean pulmonary arterial pressure, with an ED(50) of 39.0 (31.4–50.6) μg kg(−1), i.v. (geometric mean with 95% confidence limits in parentheses) compared to 1.4 (1.1–2.3) μg kg(−1), i.v., for U-46619. The maximum responses evoked by U-46619 and 8-iso-PGF(2α) were not statistically significantly different (21.0±1.0 and 25.8±1.9 mmHg at 10 μg kg(−1) of U-46619 and 630 μg kg(−1) of 8-iso-PGF(2α), respectively). 3. The TP receptor antagonist, SQ 29,548 (0.63 mg kg(−1), i.v. + 0.63 mg kg(−1) h(−1)) fully antagonised both U-46619 and 8-iso-PGF(2α)-induced pulmonary hypertensive responses. 4. Further experiments were carried out to determine whether 8-iso-PGF(2α) antagonized the pulmonary hypertensive responses evoked by U-46619, or those induced by itself, as would be predicted for a partial agonist. However, ED(10) or ED(25) doses of 8-iso-PGF(2α) (10 or 20 μg kg(−1), i.v.) failed to reduce the pulmonary hypertensive responses induced either by U-46619 or by itself. 5. The data suggest that in the pulmonary vascular bed of the rat, 8-iso-PGF(2α) acts as an agonist of high intrinsic activity at SQ 29,548-sensitive (probably TP) receptors
John, Gareth W - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the pulmonary hypertensive effects of the Isoprostane Derivative, 8-iso-PGF(2α), in the rat
1997Co-Authors: John, Gareth W, Valentin Jean-pierreAbstract:1. We analysed the pulmonary hypertensive effects of the F(2)-Isoprostane Derivative, 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), in comparison with those of the high efficacy thromboxane A(2)/prostanoid (TP) receptor agonist, U-46619, in pentobarbitone-anaesthetized, open-chest rats (n=4–15 per group). 2. 8-iso-PGF(2α) produced dose-dependent increases in mean pulmonary arterial pressure, with an ED(50) of 39.0 (31.4–50.6) μg kg(−1), i.v. (geometric mean with 95% confidence limits in parentheses) compared to 1.4 (1.1–2.3) μg kg(−1), i.v., for U-46619. The maximum responses evoked by U-46619 and 8-iso-PGF(2α) were not statistically significantly different (21.0±1.0 and 25.8±1.9 mmHg at 10 μg kg(−1) of U-46619 and 630 μg kg(−1) of 8-iso-PGF(2α), respectively). 3. The TP receptor antagonist, SQ 29,548 (0.63 mg kg(−1), i.v. + 0.63 mg kg(−1) h(−1)) fully antagonised both U-46619 and 8-iso-PGF(2α)-induced pulmonary hypertensive responses. 4. Further experiments were carried out to determine whether 8-iso-PGF(2α) antagonized the pulmonary hypertensive responses evoked by U-46619, or those induced by itself, as would be predicted for a partial agonist. However, ED(10) or ED(25) doses of 8-iso-PGF(2α) (10 or 20 μg kg(−1), i.v.) failed to reduce the pulmonary hypertensive responses induced either by U-46619 or by itself. 5. The data suggest that in the pulmonary vascular bed of the rat, 8-iso-PGF(2α) acts as an agonist of high intrinsic activity at SQ 29,548-sensitive (probably TP) receptors
Bernard Muller - One of the best experts on this subject based on the ideXlab platform.
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J012 Cyclooxygenase-2-dependent Isoprostane production in hypoxia-induced pulmonary hypertension
Archives of Cardiovascular Diseases, 2009Co-Authors: Estelle Delannoy, Arnaud Courtois, Véronique Leblais, Roger Marthan, Bernard MullerAbstract:This study investigates the contribution of contractile prostanoids in hyper-reactivity of pulmonary arteries to vasoconstrictors, in a mice model of hypoxic pulmonary arterial hypertension. Male C57BL/6 mice were exposed or not to hypobaric hypoxia (0.5 atm) for 21 days. Extrapulmonary arteries were removed and used for evaluation of vasomotor responses (using wire myograph), for expression and localisation of cyclooxygenases and thromboxane A2 (TXA2)-synthase (by western blotting and immunofluoresnce) and for release of vasoactive prostanoids (by ELISA). In pulmonary arteries from hypoxic mice (but not in those from normoxic mice), arachidonic acid (30 μM) induced a contractile effect, that was converted into relaxation in the presence of SQ29548 (0.5 μM), a thromboxane receptor (TP) antagonist. In these arteries, contraction to phenylephrine (3 μM) was enhanced about 1.8 fold increase compared to controls, in both endothelium-intact and denuded preparations. This hyper-reactivity to phenylephrine was diminished by SQ29548, by the selective COX-2 inhibitor NS398 (1 μM), but not by the phospholipase A2 inhibitor AACOCF3 (30 μM), the COX-1 inhibitor SC560 (0.1 μM) or the TXA2-synthase inhibitor furegrelate (100 μM). None of these agents affected contraction to phenylephrine in pulmonary arteries from normoxic mice. Expression of COX-1, which was found in all layers of pulmonary arteries, was decreased by chronic hypoxia as well as expression of TXA2-synthase. COX-2 expression was restricted to the medial layer of pulmonary arteries. Hypoxia decreased the release of TXA2 and the release of PGI2 from pulmonary arteries, while it increased the release of 8-iso-PGF2α (an Isoprostane Derivative that is a marker of oxidative stress). NS398 abolished hypoxia-induced elevation of 8-iso-PGF2α release from pulmonary arteries. Finally, 8-iso-PGF2α induced a contractile effect in pulmonary arteries, which was blunted by SQ29548. Moreover, 8-iso-PGF2α markedly potentiated contraction to phenylephrine. These data show that following chronic hypoxia, pulmonary arteries exhibited alterations in arachidonic acid pathway, and hyper-responsiveness to phenylephrine. The latter is likely mediated by COX-2-dependent production of 8-iso-PGF2α, which in turn activates TP receptor. Such mechanisms probably contribute to elevation in pulmonary arterial resistance in hypoxia-induced pulmonary arterial hypertension.