Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein.


:In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded prostaglandin E2 (PGE2) by 73%. Endothelium removal lowered PGI2 by 77% and PGE2 by 66%. At low oxygen tension (PO2, 40 mm Hg), PGI2 and PGE2 synthesis rose by 96% and 102%, respectively. Similarly, in endothelial cells studied at PO2 of 680 mm Hg, the synthesis of PGI2 exceeded PGE2 by 50%, and at low oxygen tension both PGI2 and PGE2 increased (89% and 64%, respectively). Endothelial cell PGI2 synthesis maximally stimulated by bradykinin, A23187, or arachidonic acid was also increased at low PO2 by 50%, 66%, and 48%, respectively. PGE2 synthesis was similarly altered, increasing by 33%, 37%, and 41%, respectively. In contrast, lowering oxygen had minimal effect on PGI2 and PGE2 synthesis with exogenous PGH2, which is the product of cyclooxygenase. Immunoblot analyses revealed that there was a 2.6-fold greater abundance of cyclooxygenase-1 protein at PO2 of 40 versus 680 mm Hg, and the increase at lower oxygen tension was inhibited by cycloheximide. The cyclooxygenase-2 isoform was not detected. Thus, attenuated oxygenation directly stimulates PGI2 and PGE2 synthesis in intrapulmonary arterial segments and endothelial cells from newborn lambs. This process is due to enhanced cyclooxygenase activity related to increased abundance of the cyclooxygenase-1 protein, and this effect may be due to increased synthesis of the enzyme protein.


Circ Res


Circulation research


North AJ,Brannon TS,Wells LB,Campbell WB,Shaul PW




Has Abstract


1994-07-01 00:00:00












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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hilfiker-Kleiner D,Hilfiker A,Fuchs M,Kaminski K,Schaefer A,Schieffer B,Hillmer A,Schmiedl A,Ding Z,Podewski E,Podewski E,Poli V,Schneider MD,Schulz R,Park JK,Wollert KC,Drexler H

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    pub_type: 杂志文章


    authors: Medley TL,Kingwell BA,Gatzka CD,Pillay P,Cole TJ

    更新日期:2003-06-13 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Latham RD,Rubal BJ,Sipkema P,Westerhof N,Virmani R,Robinowitz M,Walsh RA

    更新日期:1988-10-01 00:00:00

  • Responses of the heart to stimulation of aortic body chemoreceptors in dogs.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Karim F,Hainsworth R,Sofola OA,Wood LM

    更新日期:1980-01-01 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


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    更新日期:2000-09-29 00:00:00

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    pub_type: 杂志文章


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    更新日期:2010-02-19 00:00:00

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    pub_type: 杂志文章


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    更新日期:2008-11-07 00:00:00

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    pub_type: 杂志文章


    authors: Madsen CS,Regan CP,Hungerford JE,White SL,Manabe I,Owens GK

    更新日期:1998-05-04 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Brody JS,Vaccaro CA,Hill NS,Rounds S

    更新日期:1984-08-01 00:00:00

  • Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure.

    abstract::Membrane current abnormalities have been described in human heart failure. To determine whether similar current changes are observed in a large animal model of heart failure, we studied dogs with pacing-induced cardiomyopathy. Myocytes isolated from the midmyocardium of 13 dogs with heart failure induced by 3 to 4 wee...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Kääb S,Nuss HB,Chiamvimonvat N,O'Rourke B,Pak PH,Kass DA,Marban E,Tomaselli GF

    更新日期:1996-02-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:1999-09-17 00:00:00

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    abstract:RATIONALE:Atherosclerosis proceeds through a multistep reaction that begins with endothelial injury caused by a host of stress signals, among which oxidized low-density lipoprotein (oxLDL) plays a critical role. OxLDL disrupts normal functionality of the endothelium by upregulating adhesion molecules (eg, ICAM-1) and c...

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    authors: Fang F,Yang Y,Yuan Z,Gao Y,Zhou J,Chen Q,Xu Y

    更新日期:2011-04-01 00:00:00

  • NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis.

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    pub_type: 杂志文章,评审


    authors: Grebe A,Hoss F,Latz E

    更新日期:2018-06-08 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Shepro D,Batbouta JC,Robblee LS,Carson MP,Belamarich FA

    更新日期:1975-06-01 00:00:00

  • Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Bailey JC,Watanabe AM,Besch HR Jr,Lathrop DA

    更新日期:1979-03-01 00:00:00

  • The Malaria-High Blood Pressure Hypothesis.

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    pub_type: 杂志文章,评审


    authors: Etyang AO,Smeeth L,Cruickshank JK,Scott JA

    更新日期:2016-06-24 00:00:00

  • Factor associated with neutral sphingomyelinase activation and its role in cardiac cell death.

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    journal_title:Circulation research

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    authors: O'Brien NW,Gellings NM,Guo M,Barlow SB,Glembotski CC,Sabbadini RA

    更新日期:2003-04-04 00:00:00

  • Relation between lipopolysaccharide-induced endothelial cell injury and entry of macromolecules into the rat aorta in vivo.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Penn MS,Chisolm GM

    更新日期:1991-05-01 00:00:00

  • Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice.

    abstract:RATIONALE:Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies ha...

    journal_title:Circulation research

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    authors: Sobirin MA,Kinugawa S,Takahashi M,Fukushima A,Homma T,Ono T,Hirabayashi K,Suga T,Azalia P,Takada S,Taniguchi M,Nakayama T,Ishimori N,Iwabuchi K,Tsutsui H

    更新日期:2012-09-28 00:00:00

  • Pulmonary vasodilatory action of endogenous atrial natriuretic factor in rats with hypoxic pulmonary hypertension. Effects of monoclonal atrial natriuretic factor antibody.

    abstract::We administered ascitic fluid containing atrial natriuretic factor (ANF) monoclonal antibody to rats after 3 weeks of exposure to hypoxia while the rats were still hypoxic. In additional chronically hypoxic rats, we infused synthetic rat ANF. In conscious chronically instrumented rats, after a bolus dose of 5 microgra...

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    pub_type: 杂志文章


    authors: Raffestin B,Levame M,Eddahibi S,Viossat I,Braquet P,Chabrier PE,Cantin M,Adnot S

    更新日期:1992-01-01 00:00:00

  • Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat.

    abstract::We studied the pulmonary vascular effects of prostacylin, PGI2, in the cat with intact chest under conditions of controlled blood flow. Intralobar injections of PGI2, 0.03--1 microgram, decreased arterial pressure in the perfused lobe in a dose-dependent manner. Inasmuch as lobar blood flow was held constant and left ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hyman AL,Kadowitz PJ

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  • Differential accumulation of diacyl and plasmalogenic diglycerides during myocardial ischemia.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ford DA,Gross RW

    更新日期:1989-01-01 00:00:00

  • The mechanical stress-activated serum-, glucocorticoid-regulated kinase 1 contributes to neointima formation in vein grafts.

    abstract:RATIONALE:Mechanical stress plays an important role in proliferation of venous smooth muscle cells (SMCs) in neointima, a process of formation that contributes to failure of vein grafts. However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs. OBJECTIVE:The objective of this study...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Cheng J,Wang Y,Ma Y,Chan BT,Yang M,Liang A,Zhang L,Li H,Du J

    更新日期:2010-11-12 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Boyden PA,Albala A,Dresdner KP Jr

    更新日期:1989-10-01 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Roskoski R Jr,Schmid PG,Mayer HE,Abboud FM

    更新日期:1975-04-01 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Kiuchi K,Sato N,Shannon RP,Vatner DE,Morgan K,Vatner SF

    更新日期:1993-12-01 00:00:00

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zhao G,Zhang X,Xu X,Ochoa M,Hintze TH

    更新日期:1997-06-01 00:00:00

  • Heterogeneous changes in epimyocardial microvascular size during graded coronary stenosis. Evidence of the microvascular site for autoregulation.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Kanatsuka H,Lamping KG,Eastham CL,Marcus ML

    更新日期:1990-02-01 00:00:00

  • Stress, deformation, and atelectasis of the lung.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Fung YC

    更新日期:1975-10-01 00:00:00

  • Contribution of Na(+)-Ca2+ exchange to stimulation of transient inward current by isoproterenol in rabbit cardiac Purkinje fibers.

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    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Han X,Ferrier GR

    更新日期:1995-04-01 00:00:00