Cerebrovascular effects of prostanoids: In Vitro studies in feline middle cerebral and basilar artery

Whalley, E. T.; Schilling, Lothar; Wahl, Michael

doi:10.1016/0090-6980(89)90045-2

Cited by 18 publications

(8 citation statements)

References 13 publications

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“…We considered other vasoconstrictors that can act on TXA 2 -PGH 2 receptors such as PGF 2␣ , high concentra-H247 ESTROGEN SHIFTS BRAIN VASCULAR PROSTANOID ACTIVITY tions of PGE 2 (45), and isoprostanes, which are generated from arachidonic acid by free radicals (17). Although these substances were released by cerebral arteries, their production was unaffected by estrogen treatment.…”

Section: H245mentioning

confidence: 99%

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

Ospina

Duckles

Krause

2003

American Journal of Physiology-Heart and Circulatory Physiology

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We have previously shown that estrogen treatment increases cerebrovascular cyclooxygenase-1, prostacyclin synthase, and production of prostacyclin. Therefore, vascular tone and prostanoid production were measured to investigate functional consequences of estrogen exposure. Middle cerebral arteries were isolated from ovariectomized female Fischer-344 rats with or without chronic in vivo 17beta-estradiol treatment. In vivo 17beta-estradiol treatment increased cerebral artery diameter; functional endothelium was required for expression of these differences. The nonspecific cyclooxygenase inhibitor indomethacin constricted, whereas arachidonic acid dilated, cerebral arteries from estrogen-treated animals. Estrogen exposure increased production of prostacyclin by cerebral arteries. Conversely, in estrogen-deficient animals, indomethacin dilated and arachidonic acid constricted cerebral blood vessels. This correlated with vasorelaxation following inhibition of the thromboxane-endoperoxide receptor with SQ-29548 but not after selective blockade of thromboxane synthase with furegrelate, suggesting prostaglandin endoperoxide (i.e., PGH2) activity. Removal of the endothelium or selective blockade of cyclooxygenase-1 with SC-560 abolished estrogen-mediated differences in the effects of arachidonate on vessel diameter and on prostacyclin production by cerebral arteries. These data suggest 17beta-estradiol decreases cerebrovascular tone by shifting the primary end product of the endothelial cyclooxygenase-1 pathway from the constrictor prostaglandin PGH2 to the vasodilator prostacyclin. These effects of estrogen may contribute to the heightened thromboresistance and enhanced cerebral blood flow documented in pre-versus postmenopausal women.

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Section: H245mentioning

confidence: 99%

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

Ospina

Duckles

Krause

2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…P rostaglandin E 2 (PGE 2 ) is an important bioactive lipid with pleiotropic effects in the central nervous system (CNS) through a paracrine action on neurons (Li et al, 2008), glial cells (Chaudhry et al, 2008;Levi et al, 1998), and smooth muscle cells of brain blood vessels (Baenziger et al, 1979;Whalley et al, 1989). The homeostatic PGE 2 level is usually low and it is mainly maintained by the sequential action of the ubiquitous enzymes prostaglandin-endoperoxide synthase 1 (PTGS1, also known as COX-1), prostaglandin E synthase 2 (PTGES2, also known as mPGES-2), and PTGES3 (also known as cPGES) (Tanioka et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

CCAAT/Enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E₂production in activated microglial cells

Straccia

Dentesano

Valente

et al. 2013

Glia

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The eicosanoid prostaglandin E2 (PGE2) plays important roles in neuroinflammation and it is produced by the sequential action of the enzymes cyclooxygenase‐2 (COX‐2) and prostaglandin E synthase (PTGES). The expression of both enzymes and the production of PGE2 are increased in neuroinflammation. The objective of this study was to elucidate whether the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) regulates the expression of prostaglandin synthesis enzymes in neuroinflammation. To this aim, the expression of these enzymes in wild‐type and C/EBPβ‐null mice was analyzed in vitro and in vivo. In mixed glial cultures, lipopolysaccharide (LPS) ± interferon γ (IFN‐γ) induced C/EBPβ binding to COX‐2 and PTGES promoters. LPS ± IFN‐γ‐induced increases in PTGES expression and in PGE2 production in mixed glial and microglial cultures were abrogated in the absence of C/EBPβ. Also, increased brain PTGES expression induced by systemic LPS administration was markedly reduced in C/EBPβ‐null mice. In contrast to PTGES, the induction of COX‐2 expression in vitro or in vivo was not markedly affected by the absence of C/EBPβ. These results demonstrate that C/EBPβ regulates PTGES expression and PGE2 production by activated microglial cells in vitro and point to C/EBPβ as a regulator of PTGES expression in vivo in the inflamed central nervous system. Altogether, these findings strengthen the proposed role of C/EBPβ as a key player in the orchestration of neuroinflammatory gene response. GLIA 2013;61:1607–1619

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“…The effects of prostanoids on isolated cerebral blood vessels have been examined previously, but considerable species differences have been reported. PGE 2 has been demonstrated to weakly relax 5‐HT precontracted feline basilar and middle cerebral arteries ( Whalley et al , 1989 ), but to contract canine, rabbit and human basilar arteries ( Nakagomi et al , 1988 ; Parsons & Whalley, 1989). Despite potential experimental protocol and species differences, these data may suggest that distinct populations of prostanoid receptors are found in different vascular regions, as illustrated by differences in vasoconstrictor 5‐HT receptors present in the macro and microcirculation.…”

Section: Introductionmentioning

confidence: 99%

EP₄ prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries

Davis¹,

Murdoch²,

Ali³

et al. 2004

British J Pharmacology

110

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1 Dilatation of the cerebral vasculature is recognised to be involved in the pathophysiology of migraine. Furthermore, elevated levels of prostaglandin E 2 (PGE 2 ) occur in the blood, plasma and saliva of migraineurs during an attack, suggestive of a contributory role. In the present study, we have characterised the prostanoid receptors involved in the relaxation and contraction of human middle cerebral arteries in vitro. 2 In the presence of indomethacin (3 mM) and the TP receptor antagonist GR32191 (1 mM), PGE 2 was found to relax phenylephrine precontracted cerebral arterial rings in a concentration-dependent manner (mean pEC 50 8.070.1, n ¼ 5). 3 Establishment of a rank order of potency using the EP 4 4EP 2 agonist 11-deoxy PGE 1 , and the EP 2 4EP 4 agonist PGE 1 -OH (mean pEC 50 of 7.670.1 (n ¼ 6) and 6.470.1 (n ¼ 4), respectively), suggested the presence of functional EP 4 receptors. Furthermore, the selective EP 2 receptor agonist butaprost at concentrations o1 mM failed to relax the tissues. 4 Blockade of EP 4 receptors with the EP 4 receptor antagonists AH23848 and EP 4 A caused significant rightward displacements in PGE 2 concentration-response curves, exhibiting pA 2 and pK B values of 5.770.1, n ¼ 3, and 8.4, n ¼ 3, respectively. 5 The IP receptor agonists iloprost and cicaprost relaxed phenylephrine precontracted cerebral arterial rings (mean pEC 50 values 8.370.1 (n ¼ 4) and 8.170.1 (n ¼ 9), respectively). In contrast, the DP and FP receptor agonists PGD 2 and PGF 2a failed to cause appreciable relaxation or contraction at concentrations of up to 30 mM. In the absence of phenylephrine contraction and GR32191, the TP receptor agonist U46619 caused concentration-dependent contraction of cerebral artery (mean pEC 50 7.470.3, n ¼ 3). 6 These data demonstrate the presence of prostanoid EP 4 receptors mediating PGE 2 vasodilatation of human middle cerebral artery. IP receptors mediating relaxation and TP receptors mediating contraction were also functionally demonstrated.

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Cerebrovascular effects of prostanoids: In Vitro studies in feline middle cerebral and basilar artery

Cited by 18 publications

References 13 publications

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

CCAAT/Enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E₂production in activated microglial cells

EP₄ prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries

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Cerebrovascular effects of prostanoids: In Vitro studies in feline middle cerebral and basilar artery

Cited by 18 publications

References 13 publications

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

17β-Estradiol decreases vascular tone in cerebral arteries by shifting COX-dependent vasoconstriction to vasodilation

CCAAT/Enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E2production in activated microglial cells

EP4 prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries

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Product

Resources

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CCAAT/Enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E₂production in activated microglial cells

EP₄ prostanoid receptor‐mediated vasodilatation of human middle cerebral arteries