The role of prostaglandin E and thromboxane-prostanoid receptors in the response to prostaglandin E2 in the aorta of Wistar Kyoto rats and spontaneously hypertensive rats

Tang, E.; Jensen, Boye L.; Skøtt, Ole; Leung, George Pak-Heng; Félétou, Michel; Man, Ryk; Vanhoutte, Paul M.

doi:10.1093/cvr/cvm112

Cited by 60 publications

(71 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PGE 2 -induced relaxation of the chicken DA was abolished by AH6809 suggesting the involvement of EP receptors. However, AH6809 is a non selective EP receptor antagonist, which may also block DP and TP receptors (Tang et al 2008). Accordingly, we observed that AH6809 impaired the contraction induced by U46619.…”

Section: Discussionmentioning

confidence: 57%

“…This is consistent with a stimulatory action of PGE 2 on TP receptors. The PGE 2 promiscuous interaction with TP receptors, especially at concentrations higher than 1 M, has also been observed in several vascular tissues including human umbilical arteries (Boersma et al 1999) and veins (Daray et al 2003), human uterine arteries (Baxter et al 1995) and aorta of the spontaneously hypertensive rat (Tang et al 2008). An alternative explanation for the eVects of SQ29,548 on PGE2-induced relaxation might be the blockade of a baseline TxA2-or isoprostaneinduced tone (Gonzalez-Luis et al 2005), allowing greater relaxatory actions of PGE on its dilatory receptors.…”

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

et al. 2008

View full text Add to dashboard Cite

Prostaglandin E 2 (PGE 2 ) is the major vasodilator prostanoid of the mammalian ductus arteriosus (DA). In the present study we analyzed the response of isolated DA rings from 15-, 19-and 21-day-old chicken embryos to PGE 2 and other vascular smooth muscle relaxing agents acting through the cyclic AMP signaling pathway. PGE 2 exhibited a relaxant response in the 15-day DA, but not in the 19-and 21-day DA. Moreover, high concentrations of PGE 2 (¸3 M in 15-day and ¸1 M in 19-day and 21-day DA) induced contraction of the chicken DA. The presence of the TP receptor antagonist SQ29,548, unmasked a relaxant eVect of PGE 2 in the 19-and 21-day DA and increased the relaxation induced by PGE 2 in the 15-day DA. The presence of the EP receptor antagonist AH6809 abolished PGE 2 -mediated relaxation. The relaxant responses induced by PGE 2 and the -adrenoceptor agonist isoproterenol, but not those elicited by the adenylate cyclase activator forskolin or the phosphodiesterase 3 inhibitor milrinone, decreased with maturation. High oxygen concentrations (95%) decreased the relaxation to PGE 2 . The relaxing potency and eYcacy of isoproterenol and milrinone were higher in the pulmonary than in the aortic side of the DA, whereas no regional diVerences were found in the response to PGE 2 . We conclude that, in contrast to the mammalian situation, PGE 2 is a weak relaxant agent of the chicken DA and, with advancing incubation, it even stimulates TP vasoconstrictive receptors.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 83%

Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The EP4 receptor is expressed in a variety of arteries and veins. Expression has been shown in the great artery, e.g., the adult aorta in humans (Cao et al, 2012;Yokoyama et al, 2012), mice (Rutkai et al, 2009), and rats (Tang et al, 2008). Small arteries and veins also express EP4, including the cerebral artery (Davis et al, 2004;Maubach et al, 2009), renal arteriole (Purdy and Arendshorst, 2000), pulmonary vein (Foudi et al, 2008), and saphenous vein (Coleman et al, 1994a).…”

Section: Biologic Function and Diseasesmentioning

confidence: 99%

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

217

257

View full text Add to dashboard Cite

“…15 To ascertain the contribution of TP receptors to endothelial dysfunction, concentration-response curves to ACh were also repeated after 30-minute preincubation with SQ-29548 (1 mol/L; TP receptor antagonist). 16 The participation of thromboxane (TX) A 2 to vascular reactivity was assessed by testing ACh in the presence of ozagrel, a TX synthase inhibitor (1 mol/L). 17 To assess the influence of ROS on endothelial function, the responses to ACh were determined after 30-minute incubation with ascorbic acid (100 mol/L).…”

Section: Influence Of Cox-1 and Cox-2 Activity Tp Receptors And Rosmentioning

confidence: 99%

Atorvastatin Prevents Endothelial Dysfunction in Mesenteric Arteries From Spontaneously Hypertensive Rats

et al. 2009

View full text Add to dashboard Cite

Abstract-We investigated the effect of atorvastatin on cyclooxygenase (COX) contribution to endothelial dysfunction in spontaneously hypertensive rat (SHR) mesenteric resistance arteries. Atorvastatin (10 mg/kg per day, oral gavage) or its vehicle was administered for 2 weeks to male SHR or Wistar-Kyoto rats. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In Wistar-Kyoto rats, relaxation to acetylcholine was inhibited by N G -nitro-Larginine methyl ester and unaffected by SC-560 (COX-1 inhibitor), DuP-697 (COX-2 inhibitor), or ascorbic acid. In SHRs, the response to acetylcholine was attenuated, less sensitive to N G -nitro-L-arginine methyl ester, unaffected by SC-560, and enhanced by DuP-697 or SQ-29548 (thromboxane-prostanoid receptor antagonist) to a similar extent. Endothelium-dependent relaxation was normalized by ascorbic acid or apocynin (NADPH oxidase inhibitor), which also restored the inhibition by N G -nitro-L-arginine methyl ester. In atorvastatin-treated SHRs, relaxation to acetylcholine was normalized, fully sensitive to N G -nitro-L-arginine methyl ester, and not affected by SC-560, DuP-697, SQ 29548, or antioxidants. Dihydroethidium assay showed an increased intravascular superoxide generation in SHRs, which was abrogated by atorvastatin. RT-PCR revealed a COX-2 induction in SHR arteries, which was downregulated by atorvastatin. The release of prostacyclin and 8-isoprostane was higher from SHR than Wistar-Kyoto mesenteric vessels. COX-2 inhibition and apocynin decreased 8-isoprostane without affecting prostacyclin levels. Atorvastatin increased phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS 1177 , and inducible NO synthase levels in SHR mesenteric vessels and decreased 8-isoprostane release. In conclusion, COX-2-derived 8-isoprostane contributes to endothelial dysfunction in SHR mesenteric arteries. Atorvastatin restores NO availability by increasing phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS 1177 , and inducible NO synthase levels and by abrogating vascular NADPH oxidase-driven superoxide production, which also results in a downregulation of COX-2-dependent 8-isoprostane generation. Key Words: cell signaling Ⅲ endothelium Ⅲ microcirculation Ⅲ oxidant stress Ⅲ NO G enetic hypertension is characterized by vascular endothelial dysfunction resulting mainly from increased generation of reactive oxygen species (ROS), which, in turn, cause NO breakdown. 1,2 It is accepted that such endothelial dysfunction is implicated in the pathogenesis of atherosclerosis, leading to an increased risk of cardiovascular events. 3 There is evidence indicating that cyclooxygenase (COX)-derived prostanoids are also involved in endothelial dysfunction. In particular, studies in spontaneously hypertensive rats (SHR) have shown that COX-2 can produce contracting prostanoids, which act on thromboxane-prostanoid (TP) receptors to maintain a pathological modulation of vascular responses. 4 -7 The ROS excess is hypothesized as 1 possible mech...

show abstract

The role of prostaglandin E and thromboxane-prostanoid receptors in the response to prostaglandin E2 in the aorta of Wistar Kyoto rats and spontaneously hypertensive rats

Cited by 60 publications

References 44 publications

Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

The Prostanoid EP4 Receptor and Its Signaling Pathway

Atorvastatin Prevents Endothelial Dysfunction in Mesenteric Arteries From Spontaneously Hypertensive Rats

Contact Info

Product

Resources

About