S 18886, a New Thromboxane (TP)-Receptor Antagonist Is the Active Isomer of S 18204 in All Species, Except in the Guinea-Pig

Simonet, Serge; Descombes, Jean-Jacques; Vallez, Marie‐Odile; Dubuffet, Thierry; Lavielle, Gilbert; Verbeuren, Tony J.

doi:10.1007/978-1-4899-1810-9_35

Cited by 43 publications

(31 citation statements)

References 6 publications

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“…S18886 (Simonet et al, 1997), a selective blocker of thromboxane prostanoid receptors, did not reduce the fluorescence in the preparation with endothelium. These findings concur with the results in the vascular functional study, confirming the contribution of oxygen-derived free radicals in the endothelium-dependent contractions.…”

Section: Discussionmentioning

confidence: 78%

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Shi

Man

et al. 2007

British J Pharmacology

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Background and purpose:The present experiments were designed to study the contribution of oxygen-derived free radicals to endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes. Experimental approach: Rings with and without endothelium were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals in the endothelium was measured with 2 0 ,7 0 -dichlorodihydrofluorescein diacetate using confocal microscopy. The presence of protein was measured by western blotting. Key results: In the presence of L-NAME, the calcium ionophore A23187 induced larger endothelium-dependent contractions in femoral arteries from diabetic rats. Tiron, catalase, deferoxamine and MnTMPyP, but not superoxide dismutase reduced the response, suggesting that oxygen-derived free radicals are involved in the endothelium-dependent contraction. In the presence of L-NAME, A23187 increased the fluorescence signal in femoral arteries from streptozotocin-treated, but not in those from control rats, confirming that the production of oxygen-derived free radicals contributes to the enhanced endotheliumdependent contractions in diabetes. Exogenous H 2 O 2 caused contractions in femoral arterial rings without endothelium which were reduced by deferoxamine, indicating that hydroxyl radicals contract vascular smooth muscle and thus could be an endothelium-derived contracting factor in diabetes. The reduced presence of Mn-SOD and the decreased activity of catalase in femoral arteries from streptozotocin-treated rats demonstrated the presence of a redox abnormality in arteries from rats with diabetes. Conclusions and implications: These findings suggest that the redox abnormality resulting from diabetes increases oxidative stress which facilitates and/or causes endothelium-dependent contractions.

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Section: Discussionmentioning

confidence: 78%

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Shi

Man

et al. 2007

British J Pharmacology

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“…S18886 (Simonet et al, 1997), a selective antagonist for TP-receptors, abolished the contraction, whereas indomethacin, an inhibitor of cyclooxygenases, not only prevented but also reversed it to a relaxation. This then strongly suggests that the endothelium-derived contracting factor involved is produced by cyclooxygenase and activates TP-receptors.…”

Section: Discussionmentioning

confidence: 95%

Augmented Endothelium-Derived Hyperpolarizing Factor-Mediated Relaxations Attenuate Endothelial Dysfunction in Femoral and Mesenteric, but Not in Carotid Arteries from Type I Diabetic Rats

Shi

Ku²,

Man³

et al. 2006

J Pharmacol Exp Ther

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Individual vascular beds exhibit differences in vascular reactivity. The present study investigates the effects of streptozotocininduced type I diabetes on endothelium-dependent responses of rat carotid, femoral, and mesenteric arteries. Rings with and without endothelium, suspended in organ chambers for isometric tension recording, were contracted with phenylephrine and exposed to increasing concentrations of acetylcholine. In carotid and femoral arteries, acetylcholine produced concentration-and endothelium-dependent relaxations that were abolished by N -nitro-L-arginine methyl ester (L-NAME; specific nitric-oxide synthase inhibitor) and were impaired slightly in preparations from streptozotocin-treated rats (STZ-rats). This impairment could be prevented by L-arginine. In femoral arteries incubated with L-NAME, acetylcholine caused endotheliumdependent contractions that were abolished by 3-[(6-amino-(4-chlorobenzensulfonyl)-2-methyl-5,6,7,8-tetrahydronapht]-1-yl) propionic acid (S18886) (antagonist of thromboxane A 2 /prostaglandins H 2 -receptors) and reversed to relaxation by indomethacin (inhibitor of cyclooxygenase). The latter relaxation was inhibited by charybdotoxin plus apamin, suggesting a role of endothelium-dependent hyperpolarizing factor (EDHF). This EDHF-mediated component was augmented slightly in arteries from STZ-rats. In mesenteric arteries, relaxations to acetylcholine were only partially inhibited by L-NAME, and the L-NAMEresistant component was abolished by charybdotoxin plus apamin. In the mesenteric arteries from STZ-rats, L-NAME-sensitive relaxations to acetylcholine were reduced and the EDHFcomponent was augmented. These findings demonstrate a marked heterogeneity in endothelium-dependent responses in rat arteries and their differential adaptation in the course of type I diabetes. In particular, the EDHF-mediated component not only compensates for the reduced bioavailability of nitric oxide in the femoral and mesenteric artery but also counteracts the augmented endothelium-dependent contractions in the former.The endothelial cells release both endothelium-derived relaxing factors and endothelium-derived contracting factors (EDCFs), which control the tone of the underlying smooth muscle. Endothelium-derived relaxing factors include NO, prostacyclin, and several endothelium-derived hyperpolarizing factors (EDHFs). Different vascular beds, exposed to varying local and neurohumoral influences, exhibit a marked heterogeneity in vascular responsiveness (Vanhoutte, 1978;Lü scher and Vanhoutte, 1990;Feletou and Vanhoutte, 2006). NO is a major contributor to endothelium-dependent relaxations in large conduit arteries, whereas endothelium-derived hyperpolarizing factor(s) play a predominant role in small arteries (Nagao et al., 1992;Shimokawa et al., 1996). Diabetes mellitus is characterized by hyperglycemia resulting from a defective secretion and/or action of insulin. Data on the impairment of endothelial function caused by type I diabetes are controversial. Thus, in blood vessels from...

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“…In particular, histamine evokes a biphasic response in arterioles from WT mice and a constrictor response in the eNOS Ϫ / Ϫ mouse (25). Mast cells are present along resistance arteries from the hamster cheek pouch (8), and they influence vascular resistance by releasing histamine and thromboxane A 2 (31). Mast cells are also present in small mesenteric arteries (17).…”

Section: Discussionmentioning

confidence: 99%

Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

Schjerning

Uhrenholt

Svenningsen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Schjerning J, Uhrenholt TR, Svenningsen P, Vanhoutte PM, Skøtt O, Jensen BL, Hansen PB. Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse. Am J Physiol Heart Circ Physiol 304: H1094 -H1102, 2013. First published February 8, 2013 doi:10.1152/ajpheart.00524.2012.-In arterioles, aldosterone counteracts the rapid dilatation (recovery) following depolarization-induced contraction. The hypothesis was tested that this effect of aldosterone depends on cyclooxygenase (COX)-derived products and/or nitric oxide (NO) synthase (NOS) inhibition. Recovery of the response to high K ϩ was observed in mesenteric arteries of wild-type and COX-2 Ϫ/Ϫ mice but it was significantly diminished in preparations from endothelial NOS (eNOS) Ϫ/Ϫ mice. Aldosterone pretreatment inhibited recovery from wild-type and COX-2 Ϫ/Ϫ mice. The NO donor sodium nitroprusside (SNP) restored recovery in arteries from eNOS Ϫ/Ϫ mice, and this was inhibited by aldosterone. Actinomycin-D abolished the effect of aldosterone, indicating a genomic effect. The effect was blocked by indomethacin and by the COX-1 inhibitor valeryl salicylate but not by NS-398 (10 Ϫ6 mol/l) or the TP-receptor antagonist S18886 (10 Ϫ7 mol/l). The effect of aldosterone on recovery in arteries from wild-type mice and the SNPmediated dilatation in arteries from eNOS Ϫ/Ϫ mice was inhibited by the histamine H2 receptor antagonist cimetidine. RT-PCR showed expression of mast cell markers in mouse mesenteric arteries. The adventitia displayed granular cells positive for toluidine blue vital stain. Confocal microscopy of live mast cells showed loss of quinacrine fluorescence and swelling after aldosterone treatment, indicating degranulation. RT-PCR showed expression of mineralocorticoid receptors in mesenteric arteries and in isolated mast cells. These findings suggest that aldosterone inhibits recovery by stimulation of histamine release from mast cells along mesenteric arteries. The resulting activation of H2 receptors decreases the sensitivity to NO of vascular smooth muscle cells. Aldosterone may chronically affect vascular function through paracrine release of histamine. mast cells; mineralocorticoid; endothelial function; microcirculation CHANGES IN INTERNAL VASCULAR diameter and thus local peripheral resistance contribute to the regulation of arterial blood pressure and the distribution of blood flow to distal tissues. In renal arterioles, depolarization-elicited vasoconstriction is counter-regulated by a secondary, nitric oxide (NO)-mediated dilatation termed recovery (38). This phenomenon is associated with transfer of a calcium signal from the smooth muscle cells to the endothelial cells. Another type of rapid interference with vasoconstrictor responses occurs after 5 min of exposure to aldosterone, which inhibits depolarization-induced constriction in the afferent arteriole also in a NO-dependent manner (37). Longer (50 min) exposure of renal arterioles to aldosterone significantly inhibits recovery (37).Aldoste...

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S 18886, a New Thromboxane (TP)-Receptor Antagonist Is the Active Isomer of S 18204 in All Species, Except in the Guinea-Pig

Cited by 43 publications

References 6 publications

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

Augmented Endothelium-Derived Hyperpolarizing Factor-Mediated Relaxations Attenuate Endothelial Dysfunction in Femoral and Mesenteric, but Not in Carotid Arteries from Type I Diabetic Rats

Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

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