Prostaglandin E2 modulation of blood pressure homeostasis: Studies in rodent models

Swan, Christina E.; Breyer, Richard M.

doi:10.1016/j.prostaglandins.2011.07.001

Cited by 28 publications

(24 citation statements)

References 39 publications

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“…HWESASXX (a peptide linked to inflammation and positively associated with blood pressure) (38), and 2 eicosanoids (prostaglandin E 2 and leukotriene B 4 ) decreased with sodium restriction. Eicosanoids are known to play a role in the regulation of blood pressure (39).…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

Derkach

Sampson

Joseph

et al. 2017

The American Journal of Clinical Nutrition

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Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies. Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure. Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high-and low-sodium interventions and in 46 participants at the end of their high-and medium-sodium interventions (N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups. Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, g-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate #0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold (P , 10 25 ). Adjustment for coinciding change in blood pressure did not substantively alter the association for the top-ranked metabolites. Conclusion: Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and g-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608.

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Section: Discussionmentioning

confidence: 99%

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

Derkach

Sampson

Joseph

et al. 2017

The American Journal of Clinical Nutrition

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“…PGE 2 regulates vascular tone through activation of its four G-protein coupled receptors, EP1-EP4 (reviewed in (Swan and Breyer, 2011)). Studies in ex vivo preparations and in vivo have shown that the Gαs-coupled EP2 and EP4 receptors are vasodilatory, whereas the Gαq-coupled EP1 and Gαi-coupled EP3 receptor promote vasoconstriction.…”

Section: Introductionmentioning

confidence: 99%

Protection by vascular prostaglandin E2 signaling in hypoxic–ischemic encephalopathy

Taniguchi

Anacker

Wang

et al. 2014

Experimental Neurology

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Hypoxic ischemic encephalopathy (HIE) in neonates is a leading cause of neurological impairment. Significant progress has been achieved investigating the pathologic contributions of excitotoxicity, oxidative stress, and neuroinflammation to cerebral injury in HIE. Less extensively investigated has been the contribution of vascular dysfunction, and whether modulation of cerebral perfusion may improve HIE outcome. Here, we investigated the function of the prostaglandin E2 (PGE2) EP4 receptor, a vasoactive Gαs-protein coupled receptor (GPCR), in rodent models of neonatal HIE. The function of PGE2 signaling through the EP4 receptor was investigated using pharmacologic and conditional knockout genetic strategies in vivo in rodent models of HIE. Pharmacologic activation of the EP4 receptor with a selective agonist was significantly cerebroprotective both acutely and after 7 days. Measurement of cerebral perfusion during and after hypoxia-ischemia demonstrated that EP4 receptor activation improved cerebral perfusion in both the contralateral and ipsilateral hypoxic-ischemic hemispheres. To test whether vascular EP4 signaling exerted a critical function in HIE injury, cell specific conditional knockout mouse pups were generated in which endothelial EP4 receptor was selectively deleted postnatally. VE-Cadherin Cre-ERT2;EP4lox/lox pups demonstrated significant increases in cerebral injury as compared to VE-Cadherin CreERT2;EP4+/+ control littermates, indicating that endothelial EP4 signaling is protective in HIE. Our findings identify vascular PGE2 signaling through its EP4 receptor as protective in HIE. Given the pharmacologic accessibility of endothelial EP4 GPCRs, these data support further investigation into novel approaches to target cerebral perfusion in neonatal HIE.

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“…Prostaglandin E 2 (PGE 2 ) mediates pain and inflammation and has been implicated in the regulation of blood pressure 1 , thrombosis 2, 3 and atherogenesis 4 . It is generated from a prostaglandin (PG) substrate, PGH 2 , itself formed by the metabolism of arachidonic acid by PGG/H synthase enzymes, commonly known as cyclooxygenases (COXs).…”

Section: Introductionmentioning

confidence: 99%

Cell Selective Cardiovascular Biology of Microsomal Prostaglandin E Synthase-1

Chen

Yang

et al. 2013

Circulation

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Background Global deletion of microsomal prostaglandin E synthase (mPGES) -1 in mice attenuates the response to vascular injury without a predisposition to thrombogenesis or hypertension. However, enzyme deletion results in cell specific differential utilization by prostaglandin (PG) synthases of the accumulated PGH2 substrate. Here, we generated mice deficient in mPGES-1 in vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and myeloid cells further to elucidate the cardiovascular function of this enzyme. Methods and Results VSMC and EC mPGES-1 deletion did not alter blood pressure at baseline or in response to a high salt diet. The propensity to evoked macrovascular and microvascular thrombogenesis was also unaltered. However, both VSMC and EC mPGES-1 deficient mice exhibited a markedly exaggerated neointimal hyperplastic response to wire injury of the femoral artery compared to their littermate controls. The hyperplasia was associated with increased proliferating cell nuclear antigen (PCNA) and tenascin-C (TN-C) expression. In contrast, the response to injury was markedly suppressed by myeloid cell depletion of mPGES-1 with decreased hyperplasia, leukocyte infiltration and expression of PCNA and TN-C. Conditioned medium derived from mPGES-1 deficient macrophages less potently induced VSMC proliferation and migration than that from wild type macrophages. Conclusion Deletion of mPGES-1 in the vasculature and myeloid cells differentially modulates the response to vascular injury, implicating macrophage mPGES-1 as a cardiovascular drug target.

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Prostaglandin E2 modulation of blood pressure homeostasis: Studies in rodent models

Cited by 28 publications

References 39 publications

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

Protection by vascular prostaglandin E2 signaling in hypoxic–ischemic encephalopathy

Cell Selective Cardiovascular Biology of Microsomal Prostaglandin E Synthase-1

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