Larger endothelium-dependent contractions in iliac arteries of adult SHRs are attributed to differential downregulation of TP and EP3 receptors in the vessels of WKYs and SHRs during the transition from adolescence to adulthood

Zhang, Yingzhan; Luo, Wei; Li, Hui; Yu, Gang; Liu, Hongjun; Leng, Jing; Ge, Jiahui; Zeng, Ruhui; Guo, Tingting; Yin, Yehu; Zhou, Yingbi; Liu, Bin

doi:10.1016/j.ejphar.2020.173828

Cited by 7 publications

(15 citation statements)

References 32 publications

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“…Also, it remains to be determined whether the weak vasoconstrictor effect of PGI 2 reported in some humans vessels is due to limited vessels studied or the scarce vasodilator effect of low concentrations of PGI 2 shown on some human vascular beds results from the compromising effect of EP3 as we have noted in rat mesenteric resistance arteries 63,79,128 . It needs to be pointed out that although the vasoconstrictor effect of PGI 2 in some vascular beds might be subtle under normal conditions it can significantly increase in diseases 79,86 …”

Section: Questions Remaining To Be Resolved or Limitations Of Results Obtained From Genetically Altered Micementioning

confidence: 87%

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Liu

Zhou

2021

The FASEB Journal

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Section: Questions Remaining To Be Resolved or Limitations Of Results Obtained From Genetically Altered Micementioning

confidence: 87%

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Liu

Zhou

2021

The FASEB Journal

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“…Similarly, other prior studies suggested that IP, EP, FP, or DP might be responsible for the vasodilator effect of PGF 2α 33–36 . However, these results were obtained with prostanoids receptor agonists or antagonists, which are commonly associated with non‐selective effects 4,37–40 . As a result, the exact receptor(s) involved in the dilator activity of PGF 2α still requires further investigation.…”

Section: Discussionmentioning

confidence: 87%

“…[33][34][35][36] Notably, many prostanoid receptor antagonists or agonists have been recognized to have effects independent of their intended targets. 4,[37][38][39][40] There is thus a pressing need to verify whether the depressor effect of PGF 2α obtained after the removal of its vasoconstrictor effects is indeed mediated through FP with genetically manipulated animals. In addition, we have previously shown that in mouse renal arteries, PGF 2α is unable to evoke any vasodilator activity when its vasoconstrictor action is completely abolished by TP −/− /EP3 −/− .…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin F _2α evokes vasoconstrictor and vasodepressor activities that are both independent of the F prostanoid receptor

et al. 2022

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The F prostanoid receptor (FP), which accounts for the therapeutic effect of PGF2α in uterine atony that leads to postpartum hemorrhage and maternal morbidity, could possibly mediate vasoconstrictor effect in small or resistance arteries to elevate blood pressure that limits the clinical use of the agent in patients with cardiovascular disorders. This study aimed to test the above hypothesis with genetically altered mice. Ex vivo and in vivo experiments were performed on control wild‐type (WT) mice and mice with deficiencies in FP (FP−/−) or thromboxane (Tx)‐prostanoid receptor (the original receptor of TxA2; TP−/−), and/or those with an additional deficiency in E prostanoid receptor‐3 (one of the vasoconstrictor receptors of PGE2; EP3−/−). Here, we show that PGF2α indeed evoked vasoconstrictor responses in the above‐mentioned tissues of WT mice, which were however unaltered by FP−/−. Interestingly, such contractile responses were reversed into dilations by TP−/−/EP3−/−. A similar pattern of results was observed with the pressor effect of PGF2α under in vivo conditions. However, TP−/− alone (which could largely remove the contractile responses) did not result in relaxation to PGF2α. Also, either the ex vivo vasodilator effect or the in vivo depressor response of PGF2α obtained after the removal of TP and EP3‐mediated actions was unaltered by FP−/−. Therefore, both the ex vivo vasoconstrictor action in small or resistance arteries and the systemic pressor effect of PGF2α can reflect vasoconstrictor activities derived from the non‐FP receptors TP and EP3 outweighing a concurrently activated dilator effect, which is again independent of FP.

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“…While principally regarded as a vasodilator, PGI 2 mediates both relaxation and contraction of smooth muscle (Dusting et al, 1977 ; Liu et al, 2017 ; Moncada et al, 1976 ). PGI 2 has subsequently been identified as an endothelial‐derived contracting factor produced in response to acetylcholine within rat aorta (Gluais et al, 2005 ), mesenteric (Liu et al, 2017 ), iliac (Zhang et al, 2021 ) and renal arteries (Zhang et al, 2021 ) in a process attributed to the activation of both EP and TP prostanoid receptors. Consistent with Liu et al ( 2017 ), we show that high concentrations of iloprost‐evoked contractions were blocked by the EP 3 receptor antagonist L‐798,106.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphism in prostacyclin‐mimetic responses within rat mesenteric arteries: A novel role for K_V7.1 in shaping IP receptor‐mediated relaxation

Baldwin

Forrester

McEwan

et al. 2022

British J Pharmacology

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Background and Purpose Prostacyclin mimetics express potent vasoactive effects via prostanoid receptors that are not unequivocally defined, as to date no study has considered sex as a factor. The aim of this study was to determine the contribution of IP and EP3 prostanoid receptors to prostacyclin mimetic iloprost‐mediated responses, whether KV7.1–5 channels represent downstream targets of selective prostacyclin‐IP‐receptor agonist MRE‐269 and the impact of the oestrus cycle on vascular reactivity. Experimental Approach Within second‐order mesenteric arteries from male and female Wistar rats, we determined (1) relative mRNA transcripts for EP1–4 (Ptger1–4), IP (Ptgi) and TXA2 (Tbxa) prostanoid receptors via RT‐qPCR; (2) the effect of iloprost, MRE‐269, isoprenaline and ML277 on precontracted arterial tone in the presence of inhibitors of prostanoid receptors, potassium channels and the molecular interference of KV7.1 via wire‐myograph; (3) oestrus cycle stage via histological changes in cervical cell preparations. Key Results Iloprost evoked a biphasic response in male mesenteric arteries, at concentrations ≤100 nmol·L−1 relaxing, then contracting the vessel at concentration ≥300 nmol·L−1, a process attributed to IP and EP3 receptors respectively. Secondary contraction was absent in the females, which was associated with a reduction in Ptger3. Pharmacological inhibition and molecular interference of KV7.1 significantly attenuated relaxations produced by the selective IP receptor agonist MRE‐269 in male and female Wistar in dioestrus/metoestrus, but not pro‐oestrus/oestrus. Conclusions and Implications Stark sexual dimorphisms in iloprost‐mediated vasoactive responses are present within mesenteric arteries. KV7.1 is implicated in IP receptor‐mediated vasorelaxation and is impaired by the oestrus cycle.

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Larger endothelium-dependent contractions in iliac arteries of adult SHRs are attributed to differential downregulation of TP and EP3 receptors in the vessels of WKYs and SHRs during the transition from adolescence to adulthood

Cited by 7 publications

References 32 publications

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Prostaglandin F _2α evokes vasoconstrictor and vasodepressor activities that are both independent of the F prostanoid receptor

Sexual dimorphism in prostacyclin‐mimetic responses within rat mesenteric arteries: A novel role for K_V7.1 in shaping IP receptor‐mediated relaxation

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Larger endothelium-dependent contractions in iliac arteries of adult SHRs are attributed to differential downregulation of TP and EP3 receptors in the vessels of WKYs and SHRs during the transition from adolescence to adulthood

Cited by 7 publications

References 32 publications

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications

Prostaglandin F 2α evokes vasoconstrictor and vasodepressor activities that are both independent of the F prostanoid receptor

Sexual dimorphism in prostacyclin‐mimetic responses within rat mesenteric arteries: A novel role for KV7.1 in shaping IP receptor‐mediated relaxation

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Prostaglandin F _2α evokes vasoconstrictor and vasodepressor activities that are both independent of the F prostanoid receptor

Sexual dimorphism in prostacyclin‐mimetic responses within rat mesenteric arteries: A novel role for K_V7.1 in shaping IP receptor‐mediated relaxation