Impact of Ammonium on Syntrophic Organohalide-Respiring and Fermenting Microbial Communities

ABSTRACT Contamination with ammonium and chlorinated solvents has been reported in numerous subsurface environments, and these chemicals bring significant challenges for in situ bioremediation. Dehalococcoides mccartyi is able to reduce the chlorinated solvent trichloroethene to the nontoxic end product ethene. Fermentative bacteria are of central importance for organohalide respiration and bioremediation to provide D. mccartyi with H2, their electron donor, acetate, their carbon source, and other micronutrients. In this study, we found that high concentrations of ammonium negatively correlated with rates of trichloroethene reductive dehalogenation and fermentation. However, detoxification of trichloroethene to nontoxic ethene occurred even at ammonium concentrations typical of those found in animal waste (up to 2 g liter−1 NH4 +-N). To date, hundreds of subsurface environments have been bioremediated through the unique metabolic capability of D. mccartyi. These findings extend our knowledge of D. mccartyi and provide insight for bioremediation of sites contaminated with chlorinated solvents and ammonium. Syntrophic interactions between organohalide-respiring and fermentative microorganisms are critical for effective bioremediation of halogenated compounds. This work investigated the effect of ammonium concentration (up to 4 g liter−1 NH4 +-N) on trichloroethene-reducing Dehalococcoides mccartyi and Geobacteraceae in microbial communities fed lactate and methanol. We found that production of ethene by D. mccartyi occurred in mineral medium containing ≤2 g liter−1 NH4 +-N and in landfill leachate. For the partial reduction of trichloroethene (TCE) to cis-dichloroethene (cis-DCE) at ≥1 g liter−1 NH4 +-N, organohalide-respiring dynamics shifted from D. mccartyi and Geobacteraceae to mainly D. mccartyi. An increasing concentration of ammonium was coupled to lower metabolic rates, longer lag times, and lower gene abundances for all microbial processes studied. The methanol fermentation pathway to acetate and H2 was conserved, regardless of the ammonium concentration provided. However, lactate fermentation shifted from propionic to acetogenic at concentrations of ≥2 g liter−1 NH4 +-N. Our study findings strongly support a tolerance of D. mccartyi to high ammonium concentrations, highlighting the feasibility of organohalide respiration in ammonium-contaminated subsurface environments. IMPORTANCE Contamination with ammonium and chlorinated solvents has been reported in numerous subsurface environments, and these chemicals bring significant challenges for in situ bioremediation. Dehalococcoides mccartyi is able to reduce the chlorinated solvent trichloroethene to the nontoxic end product ethene. Fermentative bacteria are of central importance for organohalide respiration and bioremediation to provide D. mccartyi with H2, their electron donor, acetate, their carbon source, and other micronutrients. In this study, we found that high concentrations of ammonium negatively correlated with rates of trichloroethene reductive dehalogenation and fermentation. However, detoxification of trichloroethene to nontoxic ethene occurred even at ammonium concentrations typical of those found in animal waste (up to 2 g liter−1 NH4 +-N). To date, hundreds of subsurface environments have been bioremediated through the unique metabolic capability of D. mccartyi. These findings extend our knowledge of D. mccartyi and provide insight for bioremediation of sites contaminated with chlorinated solvents and ammonium.

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Transcriptomic and Proteomic Responses of the Organohalide-Respiring Bacterium Desulfoluna spongiiphila to Growth with 2,6-Dibromophenol as the Electron Acceptor

Applied and Environmental Microbiology ◽

10.1128/aem.02146-19 ◽

2019 ◽

Vol 86 (5) ◽

Cited By ~ 1

Author(s):

Jie Liu ◽

Lorenz Adrian ◽

Max M. Häggblom

Keyword(s):

Gene Expression ◽

Secondary Metabolites ◽

Electron Acceptor ◽

Marine Sponge ◽

Reductive Dehalogenation ◽

Important Process ◽

Organohalide Respiration ◽

Content Type ◽

Reductive Dehalogenase ◽

Significant Difference

ABSTRACT Organohalide respiration is an important process in the global halogen cycle and for bioremediation. In this study, we compared the global transcriptomic and proteomic analyses of Desulfoluna spongiiphila strain AA1, an organohalide-respiring member of the Desulfobacterota isolated from a marine sponge, with 2,6-dibromophenol or with sulfate as an electron acceptor. The most significant difference of the transcriptomic analysis was the expression of one reductive dehalogenase gene cluster (rdh16), which was significantly upregulated with the addition of 2,6-dibromophenol. The corresponding protein, reductive dehalogenase RdhA16032, was detected in the proteome under treatment with 2,6-dibromophenol but not with sulfate only. There was no significant difference in corrinoid biosynthesis gene expression levels between the two treatments, indicating that the production of corrinoid in D. spongiiphila is constitutive or not specific for organohalide versus sulfate respiration. Electron-transporting proteins or mediators unique for reductive dehalogenation were not revealed in our analysis, and we hypothesize that reductive dehalogenation may share an electron-transporting system with sulfate reduction. The metabolism of D. spongiiphila, predicted from transcriptomic and proteomic results, demonstrates high metabolic versatility and provides insights into the survival strategies of a marine sponge symbiont in an environment rich in organohalide compounds and other secondary metabolites. IMPORTANCE Respiratory reductive dehalogenation is an important process in the overall cycling of both anthropogenic and natural organohalide compounds. Marine sponges produce a vast array of bioactive compounds as secondary metabolites, including diverse halogenated compounds that may enrich for dehalogenating bacteria. Desulfoluna spongiiphila strain AA1 was originally enriched and isolated from the marine sponge Aplysina aerophoba and can grow with both brominated compounds and sulfate as electron acceptors for respiration. An understanding of the overall gene expression and the protein production profile in response to organohalides is needed to identify the full complement of genes or enzymes involved in organohalide respiration. Elucidating the metabolic capacity of this sponge-associated bacterium lays the foundation for understanding how dehalogenating bacteria may control the fate of organohalide compounds in sponges and their role in a symbiotic organobromine cycle.

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Versatility in Corrinoid Salvaging and Remodeling Pathways Supports Corrinoid-Dependent Metabolism in Dehalococcoides mccartyi

Applied and Environmental Microbiology ◽

10.1128/aem.02150-12 ◽

2012 ◽

Vol 78 (21) ◽

pp. 7745-7752 ◽

Cited By ~ 77

Author(s):

Shan Yi ◽

Erica C. Seth ◽

Yu-Jie Men ◽

Sally P. Stabler ◽

Robert H. Allen ◽

...

Keyword(s):

De Novo ◽

Chlorinated Solvents ◽

Axial Ligand ◽

Content Type ◽

Dehalococcoides Mccartyi ◽

Axial Ligands ◽

The Common ◽

Enzyme Cofactors ◽

Lower Ligand ◽

Insight Into

ABSTRACTCorrinoids are cobalt-containing molecules that function as enzyme cofactors in a wide variety of organisms but are produced solely by a subset of prokaryotes. Specific corrinoids are identified by the structure of their axial ligands. The lower axial ligand of a corrinoid can be a benzimidazole, purine, or phenolic compound. Though it is known that many organisms obtain corrinoids from the environment, the variety of corrinoids that can serve as cofactors for any one organism is largely unstudied. Here, we examine the range of corrinoids that function as cofactors for corrinoid-dependent metabolism inDehalococcoides mccartyistrain 195.Dehalococcoidesbacteria play an important role in the bioremediation of chlorinated solvents in the environment because of their unique ability to convert the common groundwater contaminants perchloroethene and trichloroethene to the innocuous end product ethene. All isolatedD. mccartyistrains require exogenous corrinoids such as vitamin B12for growth. However, like many other corrinoid-dependent bacteria, none of the well-characterizedD. mccartyistrains has been shown to be capable of synthesizing corrinoidsde novo. In this study, we investigate the ability ofD. mccartyistrain 195 to use specific corrinoids, as well as its ability to modify imported corrinoids to a functional form. We show that strain 195 can use only specific corrinoids containing benzimidazole lower ligands but is capable of remodeling other corrinoids by lower ligand replacement when provided a functional benzimidazole base. This study of corrinoid utilization and modification byD. mccartyiprovides insight into the array of strategies that microorganisms employ in acquiring essential nutrients from the environment.

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Dehalococcoides mccartyi Strain DCMB5 Respires a Broad Spectrum of Chlorinated Aromatic Compounds

Applied and Environmental Microbiology ◽

10.1128/aem.02597-14 ◽

2014 ◽

Vol 81 (2) ◽

pp. 587-596 ◽

Cited By ~ 36

Author(s):

Marlén Pöritz ◽

Christian L. Schiffmann ◽

Gerd Hause ◽

Ulrike Heinemann ◽

Jana Seifert ◽

...

Keyword(s):

Electron Acceptor ◽

Aromatic Compounds ◽

Lag Phase ◽

Organohalide Respiration ◽

Content Type ◽

Reductive Dehalogenase ◽

Dehalococcoides Mccartyi ◽

Type Iv ◽

Transmission Electron ◽

Almost All

ABSTRACTPolyhalogenated aromatic compounds are harmful environmental contaminants and tend to persist in anoxic soils and sediments.Dehalococcoides mccartyistrain DCMB5, a strain originating from dioxin-polluted river sediment, was examined for its capacity to dehalogenate diverse chloroaromatic compounds. Strain DCMB5 used hexachlorobenzenes, pentachlorobenzenes, all three tetrachlorobenzenes, and 1,2,3-trichlorobenzene as well as 1,2,3,4-tetra- and 1,2,4-trichlorodibenzo-p-dioxin as electron acceptors for organohalide respiration. In addition, 1,2,3-trichlorodibenzo-p-dioxin and 1,3-, 1,2-, and 1,4-dichlorodibenzo-p-dioxin were dechlorinated, the latter to the nonchlorinated congener with a remarkably short lag phase of 1 to 4 days following transfer. Strain DCMB5 also dechlorinated pentachlorophenol and almost all tetra- and trichlorophenols. Tetrachloroethene was dechlorinated to trichloroethene and served as an electron acceptor for growth. To relate selected dechlorination activities to the expression of specific reductive dehalogenase genes, the proteomes of 1,2,3-trichlorobenzene-, pentachlorobenzene-, and tetrachloroethene-dechlorinating cultures were analyzed. Dcmb_86, an ortholog of the chlorobenzene reductive dehalogenase CbrA, was the most abundant reductive dehalogenase during growth with each electron acceptor, suggesting its pivotal role in organohalide respiration of strain DCMB5. Dcmb_1041 was specifically induced, however, by both chlorobenzenes, whereas 3 putative reductive dehalogenases, Dcmb_1434, Dcmb_1339, and Dcmb_1383, were detected only in tetrachloroethene-grown cells. The proteomes also harbored a type IV pilus protein and the components for its assembly, disassembly, and secretion. In addition, transmission electron microscopy of DCMB5 revealed an irregular mode of cell division as well as the presence of pili, indicating that pilus formation is a feature ofD. mccartyiduring organohalide respiration.

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The MarR-Type Regulator Rdh2R RegulatesrdhGene Transcription in Dehalococcoides mccartyi Strain CBDB1

Journal of Bacteriology ◽

10.1128/jb.00419-16 ◽

2016 ◽

Vol 198 (23) ◽

pp. 3130-3141 ◽

Cited By ~ 7

Author(s):

Lydia Krasper ◽

Hauke Lilie ◽

Anja Kublik ◽

Lorenz Adrian ◽

Ralph Golbik ◽

...

Keyword(s):

Heterologous Expression ◽

Direct Repeat ◽

Negative Regulator ◽

Control Of Gene Expression ◽

Organohalide Respiration ◽

Content Type ◽

Reductive Dehalogenase ◽

Dehalococcoides Mccartyi ◽

Transcriptional Start Sites

ABSTRACTReductive dehalogenases are essential enzymes in organohalide respiration and consist of a catalytic subunit A and a membrane protein B, encoded byrdhABgenes. Thirty-twordhABgenes exist in the genome ofDehalococcoides mccartyistrain CBDB1. To gain a first insight into the regulation ofrdhoperons, the control of gene expression of twordhABgenes (cbdbA1453/cbdbA1452 and cbdbA1455/cbdbA1454) by the MarR-type regulator Rdh2R (cbdbA1456) encoded directly upstream was studied using heterologous expression andin vitrostudies. Promoter-lacZreporter fusions were generated and integrated into the genome of theEscherichia colihost. ThelacZreporter activities of bothrdhApromoters decreased upon transformation of the cells with a plasmid carrying therdh2Rgene, suggesting that Rdh2R acts as repressor, whereas thelacZreporter activity of therdh2Rpromoter was not affected. The transcriptional start sites of bothrdhAgenes in strain CBDB1 and/or the heterologous host mapped to a conserved direct repeat with 11- to 13-bp half-sites. DNase I footprinting revealed binding of Rdh2R to a ∼30-bp sequence covering the complete direct repeat in both promoters, including the transcriptional start sites. Equilibrium sedimentation ultracentrifugation revealed that Rdh2R binds as tetramer to the direct-repeat motif of therdhA(cbdbA1455) promoter. Using electrophoretic mobility shift assays, a similar binding affinity was found for bothrdhApromoters. In the presence of only one half-site of the direct repeat, the interaction was strongly reduced, suggesting a positive cooperativity of binding, for which unusual short palindromes within the direct-repeat half-sites might play an important role.IMPORTANCEDehalococcoides mccartyistrains are obligate anaerobes that grow by organohalide respiration. They have an important bioremediation potential because they are capable of reducing a multitude of halogenated compounds to less toxic products. We are now beginning to understand how these organisms make use of this large catabolic potential, wherebyD. mccartyiexpresses dehalogenases in a compound-specific fashion. MarR-type regulators are often encoded in the vicinity of reductive dehalogenase genes. In this study, we made use of heterologous expression andin vitrostudies to demonstrate that the MarR-type transcription factor Rdh2R acts as a negative regulator. We identify its binding site on the DNA, which suggests a mechanism by which it controls the expression of two adjacent reductive dehalogenase operons.

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Genome-Guided Identification of Organohalide-RespiringDeltaproteobacteriafrom the Marine Environment

mBio ◽

10.1128/mbio.02471-18 ◽

2018 ◽

Vol 9 (6) ◽

Cited By ~ 3

Author(s):

Jie Liu ◽

Max M. Häggblom

Keyword(s):

Marine Environment ◽

Gene Diversity ◽

Anthropogenic Activities ◽

Reductive Dehalogenation ◽

Important Process ◽

Organohalide Respiration ◽

Content Type ◽

Reductive Dehalogenase ◽

Comprehensive Survey ◽

Reductive Dehalogenase Genes

ABSTRACTOrganohalide compounds are widespread in the environment as a result of both anthropogenic activities and natural production. The marine environment, in particular, is a major reservoir of organohalides, and reductive dehalogenation is thought to be an important process in the overall cycling of these compounds.Deltaproteobacteriaare important members of the marine microbiota with diverse metabolic capacities, and reductive dehalogenation has been observed in someDeltaproteobacteria. In this study, a comprehensive survey ofDeltaproteobacteriagenomes revealed that approximately 10% contain reductive dehalogenase (RDase) genes, which are found within a common gene neighborhood. The dehalogenating potential of select RDase A-containingDeltaproteobacteriaand their gene expression were experimentally verified. ThreeDeltaproteobacteriastrains isolated from marine environments representing diverse species,Halodesulfovibrio marinisediminis,Desulfuromusa kysingii, andDesulfovibrio bizertensis, were shown to reductively dehalogenate bromophenols and utilize them as terminal electron acceptors in organohalide respiration. Their debrominating activity was not inhibited by sulfate or elemental sulfur, and these species are either sulfate- or sulfur-reducing bacteria. The analysis of RDase A gene transcripts indicated significant upregulation induced by 2,6-dibromophenol. This study extends our knowledge of the phylogenetic diversity of organohalide-respiring bacteria and their functional RDase A gene diversity. The identification of reductive dehalogenase genes in diverseDeltaproteobacteriaand confirmation of their organohalide-respiring capability suggest thatDeltaproteobacteriaplay an important role in natural organohalide cycling.IMPORTANCEThe marine environment is a major reservoir for both anthropogenic and natural organohalides, and reductive dehalogenation is thought to be an important process in the overall cycling of these compounds. Here we demonstrate that the capacity of organohalide respiration appears to be widely distributed in members of marineDeltaproteobacteria. The identification of reductive dehalogenase genes in diverseDeltaproteobacteriaand the confirmation of their dehalogenating activity through functional assays and transcript analysis in select isolates extend our knowledge of organohalide-respiringDeltaproteobacteriadiversity. The presence of functional reductive dehalogenase genes in diverseDeltaproteobacteriaimplies that they may play an important role in organohalide respiration in the environment.

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Guided cobalamin biosynthesis supports Dehalococcoides mccartyi reductive dechlorination activity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0320 ◽

2013 ◽

Vol 368 (1616) ◽

pp. 20120320 ◽

Cited By ~ 69

Author(s):

Jun Yan ◽

Jeongdae Im ◽

Yi Yang ◽

Frank E. Löffler

Keyword(s):

Reductive Dechlorination ◽

Methanosarcina Barkeri ◽

Chlorinated Ethenes ◽

Vitamin B ◽

Organohalide Respiration ◽

Dehalococcoides Mccartyi ◽

Subsurface Environments ◽

Cobalamin Biosynthesis ◽

Axenic Cultures ◽

Sporomusa Ovata

Dehalococcoides mccartyi strains are corrinoid-auxotrophic Bacteria and axenic cultures that require vitamin B 12 (CN-Cbl) to conserve energy via organohalide respiration. Cultures of D. mccartyi strains BAV1, GT and FL2 grown with limiting amounts of 1 µg l −1 CN-Cbl quickly depleted CN-Cbl, and reductive dechlorination of polychlorinated ethenes was incomplete leading to vinyl chloride (VC) accumulation. In contrast, the same cultures amended with 25 µg l −1 CN-Cbl exhibited up to 2.3-fold higher dechlorination rates, 2.8–9.1-fold increased growth yields, and completely consumed growth-supporting chlorinated ethenes. To explore whether known cobamide-producing microbes supply Dehalococcoides with the required corrinoid cofactor, co-culture experiments were performed with the methanogen Methanosarcina barkeri strain Fusaro and two acetogens, Sporomusa ovata and Sporomusa sp. strain KB-1, as Dehalococcoides partner populations. During growth with H 2 /CO 2 , M. barkeri axenic cultures produced 4.2 ± 0.1 µg l −1 extracellular cobamide (factor III), whereas the Sporomusa cultures produced phenolyl- and p -cresolyl-cobamides. Neither factor III nor the phenolic cobamides supported Dehalococcoides reductive dechlorination activity suggesting that M. barkeri and the Sporomusa sp. cannot fulfil Dehalococcoides ' nutritional requirements. Dehalococcoides dechlorination activity and growth occurred in M. barkeri and Sporomusa sp. co-cultures amended with 10 µM 5′,6′-dimethylbenzimidazole (DMB), indicating that a cobalamin is a preferred corrinoid cofactor of strains BAV1, GT and FL2 when grown with chlorinated ethenes as electron acceptors. Even though the methanogen and acetogen populations tested did not produce cobalamin, the addition of DMB enabled guided biosynthesis and generated a cobalamin that supported Dehalococcoides ' activity and growth. Guided cobalamin biosynthesis may offer opportunities to sustain and enhance Dehalococcoides activity in contaminated subsurface environments.

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Enantioselective Dechlorination of Polychlorinated Biphenyls inDehalococcoides mccartyiCG1

Applied and Environmental Microbiology ◽

10.1128/aem.01300-18 ◽

2018 ◽

Vol 84 (21) ◽

Cited By ~ 10

Author(s):

Ling Yu ◽

Qihong Lu ◽

Lan Qiu ◽

Guofang Xu ◽

Yanhong Zeng ◽

...

Keyword(s):

Polychlorinated Biphenyls ◽

Critical Role ◽

Enrichment Factors ◽

Reductive Dehalogenation ◽

Content Type ◽

Whole Cells ◽

Dehalococcoides Mccartyi ◽

Cell Extracts

ABSTRACTReductive dehalogenation mediated by organohalide-respiring bacteria plays a critical role in the global cycling of organohalides. Nonetheless, information on the dehalogenation enantioselectivity of organohalide-respiring bacteria remains limited. In this study, we report the enantioselective dechlorination of chiral polychlorinated biphenyls (PCBs) byDehalococcoides mccartyiCG1. CG1 preferentially removed halogens from the (−)-enantiomers of the three major environmentally relevant chiral PCBs (PCB174, PCB149, and PCB132), and the enantiomer compositions of the dechlorination products depended on their parent organohalides. Thein vitroassays with crude cell extracts or concentrated whole cells and thein vivoexperiments with living cells showed similar enantioselectivities, in contrast with the distinct enantiomeric enrichment factors (εER) of the substrate chiral PCBs. Additionally, these results suggest that concentrated whole cells might be an alternative to crude cell extracts inin vitrotests of reductive dehalogenation activities. The enantioselective dechlorination of other chiral PCBs that we resolved via gas chromatography further confirmed the preference of CG1 for the (−)-enantiomers.IMPORTANCEA variety of agrochemicals and pharmaceuticals are chiral. Due to the enantioselectivity in biological processes, enantiomers of chiral compounds may have different environmental occurrences, fates, and ecotoxicologies. Many chiral organohalides exist in anaerobic or anoxic soils and sediments, and organohalide-respiring bacteria play a major role in the environmental attenuation and global cycling of these chiral organohalides. Therefore, it is important to investigate the dehalogenation enantioselectivity of organohalide-respiring bacteria. This study reports the discovery of enantioselective dechlorination of chiral PCBs byDehalococcoides mccartyiCG1, which provides insights into the dehalogenation enantioselectivity ofDehalococcoidesand may shed light on future PCB bioremediation efforts to prevent enantioselective biological side effects.

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A Microcosm Treatability Study for Evaluating Wood Mulch-Based Amendments as Electron Donors for Trichloroethene (TCE) Reductive Dechlorination

Water ◽

10.3390/w13141949 ◽

2021 ◽

Vol 13 (14) ◽

pp. 1949

Author(s):

Edoardo Masut ◽

Alessandro Battaglia ◽

Luca Ferioli ◽

Anna Legnani ◽

Carolina Cruz Viggi ◽

...

Keyword(s):

Electron Donor ◽

Environmental Sustainability ◽

Reductive Dechlorination ◽

Environmental Remediation ◽

Low Cost ◽

Chlorinated Solvents ◽

Electron Donors ◽

Chlorinated Ethenes ◽

Dehalococcoides Mccartyi ◽

Wood Mulch

In this study, wood mulch-based amendments were tested in a bench-scale microcosm experiment in order to assess the treatability of saturated soils and groundwater from an industrial site contaminated by chlorinated ethenes. Wood mulch was tested alone as the only electron donor in order to assess its potential for stimulating the biological reductive dechlorination. It was also tested in combination with millimetric iron filings in order to assess the ability of the additive to accelerate/improve the bioremediation process. The efficacy of the selected amendments was compared with that of unamended control microcosms. The results demonstrated that wood mulch is an effective natural and low-cost electron donor to stimulate the complete reductive dechlorination of chlorinated solvents to ethene. Being a side-product of the wood industry, mulch can be used in environmental remediation, an approach which perfectly fits the principles of circular economy and addresses the compelling needs of a sustainable and low environmental impact remediation. The efficacy of mulch was further improved by the co-presence of iron filings, which accelerated the conversion of vinyl chloride into the ethene by increasing the H2 availability rather than by catalyzing the direct abiotic dechlorination of contaminants. Chemical analyses were corroborated by biomolecular assays, which confirmed the stimulatory effect of the selected amendments on the abundance of Dehalococcoides mccartyi and related reductive dehalogenase genes. Overall, this paper further highlights the application potential and environmental sustainability of wood mulch-based amendments as low-cost electron donors for the biological treatment of chlorinated ethenes.

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Prostacyclin and cerebral vessel relaxation

Journal of Neurosurgery ◽

10.3171/jns.1982.57.3.0334 ◽

1982 ◽

Vol 57 (3) ◽

pp. 334-340 ◽

Cited By ~ 40

Author(s):

Kamal S. Paul ◽

Eric T. Whalley ◽

Christine Forster ◽

Richard Lye ◽

John Dutton

Keyword(s):

Angiotensin Ii ◽

Arterial Spasm ◽

Cerebral Vessel ◽

Content Type ◽

Wide Range ◽

Potent Vasodilator ◽

Dose Dependent Fashion ◽

Basilar Arteries ◽

High Concentrations

✓ The authors have studied the ability of prostacyclin to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the etiology of cerebral arterial spasm. Prostacyclin (10−10 to 10−6M) caused a dose-related reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin (PG)F2α, and U-46619 (a thromboxane-A2 mimetic). These agents were tested at concentrations or volumes that produced almost maximum or maximum responses and those that produced approximately 50% of the maximum response. Contractions induced by maximum concentrations of angiotensin II and U-46619 were least affected by prostacyclin. In addition, contractions induced by thromboxane-A2 generated from guinea-pig lung were reversed in a dose-dependent fashion by prostacyclin. This ability of prostacyclin to physiologically antagonize contractions of the human basilar artery in vitro induced by high concentrations of various spasmogenic agents suggests that such a potent vasodilator agent or more stable analogue may be of value in the treatment of such disorders as cerebral arterial spasm following subarachnoid hemorrhage.

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