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  1. Article: Vascular prostaglandin synthesis: the early days.

    McGiff, J C

    Pharmacological reports : PR

    2007  Volume 58 Suppl, Page(s) 47–51

    Abstract: Prostacyclin (PGI2) and thromboxane (TxA2) labile cyclooxygenase (COX) products via PGH2 were identified in biological fluids by the ingenious application of the principle of parallel pharmacological assays developed by John Vane. Either organ perfusates ...

    Abstract Prostacyclin (PGI2) and thromboxane (TxA2) labile cyclooxygenase (COX) products via PGH2 were identified in biological fluids by the ingenious application of the principle of parallel pharmacological assays developed by John Vane. Either organ perfusates or circulating blood superfuse bioassay tissues arranged in a cascade. Tissues were selected based on specificity of responses to targeted eicosanoids. Additionally, PGI2 inhibited platelet aggregation, a finding that led to discovery of its critical anti-thrombotic activity at the blood-endothelial interface. The biological activities of PGI2 and TxA2 were the fingerprints for tracking their isolation and ultimate chemical identification. These studies were responsible for opening the modern era of vascular biology that has facilitated the development of a rational approach to the treatment of diabetic and hypertensive complications involving the arterial circulation.
    MeSH term(s) Animals ; Biological Assay/history ; Endothelium, Vascular/physiology ; Epoprostenol/biosynthesis ; Epoprostenol/history ; History, 20th Century ; Humans ; Platelet Aggregation ; Prostaglandins/biosynthesis ; Prostaglandins/history ; Thromboxane A2/biosynthesis ; Thromboxane A2/history
    Chemical Substances Prostaglandins ; Thromboxane A2 (57576-52-0) ; Epoprostenol (DCR9Z582X0)
    Language English
    Publishing date 2007-01-21
    Publishing country Switzerland
    Document type Historical Article ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186248-5
    ISSN 1734-1140
    ISSN 1734-1140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cytochrome P-450 metabolism of arachidonic acid.

    McGiff, J C

    Annual review of pharmacology and toxicology

    1991  Volume 31, Page(s) 339–369

    Abstract: The cytochrome P-450 pathway of AA metabolism is widely distributed and gives rise to a diversity of products affecting basic biological mechanisms such as vascular reactivity and transport function in critical nephron segments. P-450-AA metabolites may ... ...

    Abstract The cytochrome P-450 pathway of AA metabolism is widely distributed and gives rise to a diversity of products affecting basic biological mechanisms such as vascular reactivity and transport function in critical nephron segments. P-450-AA metabolites may participate in receptor-mediated signal transduction and may act as second messengers. The synthesis of P-450-AA products can be altered by pharmacologic probes and is affected by pathophysiological conditions. That this review has centered on the circulation and renal function should not be interpreted as minimizing the importance of P-450-AA metabolites in other organs and systems for, most assuredly, they will be shown to constitute an essential component of organ function in sites other than those addressed here.
    MeSH term(s) Animals ; Arachidonic Acid ; Arachidonic Acids/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Humans
    Chemical Substances Arachidonic Acids ; Arachidonic Acid (27YG812J1I) ; Cytochrome P-450 Enzyme System (9035-51-2)
    Language English
    Publishing date 1991
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 196587-6
    ISSN 1545-4304 ; 0362-1642
    ISSN (online) 1545-4304
    ISSN 0362-1642
    DOI 10.1146/annurev.pa.31.040191.002011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Eicosanoids and hypertension.

    McGiff, J C

    Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology

    1988  Volume 7, Issue 1, Page(s) 59–61

    MeSH term(s) Hypertension/metabolism ; Kidney Tubules/metabolism ; Loop of Henle/metabolism ; Prostaglandins/metabolism
    Chemical Substances Prostaglandins
    Language English
    Publishing date 1988-01
    Publishing country Portugal
    Document type Journal Article ; Review
    ZDB-ID 632718-7
    ISSN 0870-2551 ; 0304-4750
    ISSN 0870-2551 ; 0304-4750
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure.

    McGiff, J C / Quilley, J

    Current opinion in nephrology and hypertension

    2001  Volume 10, Issue 2, Page(s) 231–237

    Abstract: The properties of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids, vasoactivity and modulation of ion transport and mediation/modulation of the effects of vasoactive hormones, such as angiotensin II and endothelin, underscore their ... ...

    Abstract The properties of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids, vasoactivity and modulation of ion transport and mediation/modulation of the effects of vasoactive hormones, such as angiotensin II and endothelin, underscore their importance to renal vascular mechanisms and electrolyte excretion. 20-Hydroxyeicosatetraenoic acid is an integral component of renal autoregulation and tubuloglomerular feedback as well as cerebral autoregulation, eliciting vasoconstriction by the inhibition of potassium channels. Nitric oxide inhibits 20-hydroxyeicosatetraenoic acid formation, the removal of which contributes to the vasodilator effect of nitric oxide. In contrast, epoxyeicosatrienoic acids are generally vasodilatory by activating potassium channels and have been proposed as endothelium-derived hyperpolarizing factors. 20-Hydroxyeicosatetraenoic acid modulates ion transport in key nephron segments by influencing the activities of sodium--potassium-ATPase and the sodium--potassium--chloride co-transporter; however, the primacy of the various arachidonate oxygenases that generate products affecting these activities changes with age. The range and diversity of activity of 20-hydroxyeicosatetraenoic acid is influenced by its metabolism by cyclooxygenase to products affecting vasomotion and salt/water excretion. 20-Hydroxyeicosatetraenoic acid is the principal renal eicosanoid that interacts with several hormonal systems that are central to blood pressure regulation. This article reviews the most recent studies that address 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in vascular and renal tubular function and hypertension.
    MeSH term(s) Animals ; Blood Pressure/physiology ; Cerebrovascular Circulation/physiology ; Fatty Acids, Unsaturated/physiology ; Humans ; Hydroxyeicosatetraenoic Acids/physiology ; Hypertension/etiology ; Hypertension/physiopathology ; Hypertension/prevention & control ; Kidney Tubules, Proximal/physiology ; Muscle, Skeletal/blood supply ; Oxygen/metabolism ; Rats ; Renal Circulation/physiology
    Chemical Substances Fatty Acids, Unsaturated ; Hydroxyeicosatetraenoic Acids ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2001-03
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 1151092-4
    ISSN 1535-3842 ; 1062-4821 ; 1062-4813
    ISSN (online) 1535-3842
    ISSN 1062-4821 ; 1062-4813
    DOI 10.1097/00041552-200103000-00012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Is EDHF an epoxyeicosatrienoic acid?

    Quilley, J / McGiff, J C

    Trends in pharmacological sciences

    2000  Volume 21, Issue 4, Page(s) 121–124

    MeSH term(s) 8,11,14-Eicosatrienoic Acid/analogs & derivatives ; 8,11,14-Eicosatrienoic Acid/metabolism ; Acetylcholine/pharmacology ; Animals ; Biological Factors/metabolism ; Bradykinin/pharmacology ; Cytochrome P-450 Enzyme System/metabolism ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Gap Junctions/drug effects ; Gap Junctions/metabolism ; Humans ; Vasodilator Agents/pharmacology
    Chemical Substances Biological Factors ; Vasodilator Agents ; endothelium-dependent hyperpolarization factor ; 11,12-epoxy-5,8,14-eicosatrienoic acid (5DOQ38R4UW) ; Cytochrome P-450 Enzyme System (9035-51-2) ; 8,11,14-Eicosatrienoic Acid (FC398RK06S) ; Acetylcholine (N9YNS0M02X) ; Bradykinin (S8TIM42R2W)
    Language English
    Publishing date 2000-04
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 282846-7
    ISSN 1873-3735 ; 0165-6147
    ISSN (online) 1873-3735
    ISSN 0165-6147
    DOI 10.1016/s0165-6147(00)01445-0
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  6. Article: Arachidonic acid metabolism.

    McGiff, J C

    Preventive medicine

    1987  Volume 16, Issue 4, Page(s) 503–509

    Abstract: ... to epithelial cell integrity and influences tissue response to tumor-promoting agents; and (c) lipoxygenase products ...

    Abstract Arachidonic acid metabolites can act as tumor promoters and can affect growth and metastases of tumors in three ways: (a) Prostacyclin inhibits and thromboxane facilitates platelet-tumor cell interactions and, thereby, tumor cell invasiveness; (b) the cytoprotective action of prostaglandins contributes to epithelial cell integrity and influences tissue response to tumor-promoting agents; and (c) lipoxygenase products may act as tumor promoters.
    MeSH term(s) Animals ; Arachidonic Acid ; Arachidonic Acids/metabolism ; Humans ; Neoplasm Metastasis ; Neoplasms/etiology ; Neoplasms/metabolism ; Prostaglandins/biosynthesis
    Chemical Substances Arachidonic Acids ; Prostaglandins ; Arachidonic Acid (27YG812J1I)
    Language English
    Publishing date 1987-07
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 184600-0
    ISSN 1096-0260 ; 0091-7435
    ISSN (online) 1096-0260
    ISSN 0091-7435
    DOI 10.1016/0091-7435(87)90064-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: A new class of lipid mediators: cytochrome P450 arachidonate metabolites.

    Carroll, M A / McGiff, J C

    Thorax

    2000  Volume 55 Suppl 2, Page(s) S13–6

    MeSH term(s) Animals ; Arachidonic Acid/metabolism ; Cytochrome P-450 Enzyme System/physiology ; Humans ; Hydroxyeicosatetraenoic Acids/metabolism ; Lipid Metabolism ; Lung/physiology ; Muscle, Smooth/physiology ; Rabbits ; Renal Circulation/physiology
    Chemical Substances Hydroxyeicosatetraenoic Acids ; Arachidonic Acid (27YG812J1I) ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Cytochrome P-450 Enzyme System (9035-51-2)
    Language English
    Publishing date 2000-10
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 204353-1
    ISSN 1468-3296 ; 0040-6376
    ISSN (online) 1468-3296
    ISSN 0040-6376
    DOI 10.1136/thorax.55.suppl_2.s13
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  8. Article ; Online: Maternal and fetal epoxyeicosatrienoic acids in normotensive and preeclamptic pregnancies.

    Jiang, Houli / McGiff, John C / Fava, Cristiano / Amen, Gabriella / Nesta, Elisa / Zanconato, Giovanni / Quilley, John / Minuz, Pietro

    American journal of hypertension

    2012  Volume 26, Issue 2, Page(s) 271–278

    Abstract: ... with RBC EETs, C-reactive protein, and arterial stiffness. Renal production of EETs, measured as urinary ...

    Abstract Background: Epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 metabolites of arachidonic acid posited to act in the circulatory adaptation to pregnancy and the development of preeclampsia. Red blood cells (RBCs) may function as major contributors of cis- and trans-EETs.
    Methods: We performed paired analyses of EETs, dihydroxyeicosatrienoic acids (DHETs), and 20-HETE in RBCs, plasma, and urine from preeclamptic and normotensive pregnant and nonpregnant women. Blood from fetal and maternal circulation was collected. EETs, DHETs, and 20-HETE were analyzed by gas chromatography and liquid chromatography mass spectrometry. Vascular function and inflammation indices were analyzed.
    Results: Plasma EET is higher in normotensive (median, range; 9.9, 6.3-25.2ng/mL n = 29) and preeclamptic (10.9, 6.0-48.0ng/mL, n = 19) women than in nonpregnant controls (7.3, 3.7-10.2ng/mL, n = 19) and correlate with RBC EETs, C-reactive protein, and arterial stiffness. Renal production of EETs, measured as urinary DHETs, was reduced in preeclamptic (4.5, 1.6-24.5ng/mg creatinine) compared to normotensive (11.4, 1.6-44.5ng/mg creatinine) pregnancies. EETs are 3- to 5-fold greater in fetoplacental than in maternal circulation (RBCs 36.6, 13.1-69.4 vs. 12.5, 6.4-12.0ng/10(9) cells; plasma 31.6, 8.5-192.6 vs. 12.0, 6.8-48.0ng/mL). Both cis- and trans-EETs are present in fetal RBCs.
    Conclusions: RBCs contribute to elevated levels of EETs in the fetoplacental circulation. EETs may modulate systemic and fetoplacental hemodynamics in normal and preeclamptic pregnancies. Decreased renal EET generation may be associated with the development of maternal renal dysfunction and hypertension in preeclampsia.
    MeSH term(s) Adult ; C-Reactive Protein/metabolism ; Cross-Sectional Studies ; Eicosanoids/metabolism ; Erythrocytes/physiology ; Female ; Fetus/metabolism ; Hemodynamics/physiology ; Humans ; Hydroxyeicosatetraenoic Acids/metabolism ; Infant, Newborn/metabolism ; Middle Aged ; Pre-Eclampsia/metabolism ; Pre-Eclampsia/physiopathology ; Pregnancy/metabolism ; Pregnancy Complications, Cardiovascular/metabolism ; Pregnancy Complications, Cardiovascular/physiopathology ; Pregnancy Trimester, Second/metabolism ; Pregnancy Trimester, Third/metabolism ; Vascular Stiffness/physiology
    Chemical Substances Eicosanoids ; Hydroxyeicosatetraenoic Acids ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2012-12-28
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 639383-4
    ISSN 1941-7225 ; 1879-1905 ; 0895-7061
    ISSN (online) 1941-7225 ; 1879-1905
    ISSN 0895-7061
    DOI 10.1093/ajh/hps011
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  9. Article: Regulation of cyclooxygenase isoforms in the renal thick ascending limb: effects of extracellular calcium.

    Wang, D / McGiff, J C / Ferreri, N R

    Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

    2000  Volume 51, Issue 4 Pt 1, Page(s) 587–595

    Abstract: ... calcium concentration ([Ca2+]i) and protein kinase C (PKC) activity. PGE2 synthesis by mTAL cells ...

    Abstract We previously showed that primary cultures of mTAL cells express cyclooxygenase 2 (COX-2) when challenged with tumor necrosis factor alpha (TNFalpha) or phorbol myristate acetate (PMA). Moreover, expression of COX-2 was linked to decreases in TNFalpha-mediated 86Rb uptake, an in vitro correlate of natriuresis. mTAL cells in primary culture express calcium sensing receptor (CaR), a G-protein coupled receptor that senses changes in extracellular calcium concentration and ultimately increases intracellular calcium concentration ([Ca2+]i) and protein kinase C (PKC) activity. PGE2 synthesis by mTAL cells increases in a dose- and time-dependent manner after exposure of these cells to extracellular Ca2+. Similar effects were observed when cells were challenged with the CaR-selective agonist, poly-L-arginine. These data suggest that intracellular signaling mechanisms initiated via activation of CaR contribute to mTAL PGE2 synthesis. As TNF production is calcium-sensitive in some cells types, we postulate that these effects involve the regulation of COX-2 expression via a TNF-dependent mechanism. The functional implications of these studies relate to a cytokine-mediated mechanism that contributes to salt and water balance, and suggests that small changes in Ca(2+)o may contribute to the regulation of these events. The possibility that the effects of Ca(2+)o involve activation of CaR suggests that novel calcimimetic molecules might be useful in conditions, such as hypertension or other conditions, in which manipulation of extracellular fluid volume provides beneficial effects.
    MeSH term(s) Animals ; Arginine/metabolism ; Calcium/metabolism ; Calcium-Binding Proteins/metabolism ; Cells, Cultured ; Homeostasis ; Humans ; Hypercalcemia/metabolism ; Loop of Henle/enzymology ; Loop of Henle/metabolism ; Prostaglandin-Endoperoxide Synthases/metabolism ; Prostaglandins/metabolism ; Protein Isoforms
    Chemical Substances Calcium-Binding Proteins ; Prostaglandins ; Protein Isoforms ; Arginine (94ZLA3W45F) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2000-12
    Publishing country Poland
    Document type Journal Article ; Review
    ZDB-ID 1125221-2
    ISSN 1899-1505 ; 0867-5910 ; 0044-6033
    ISSN (online) 1899-1505
    ISSN 0867-5910 ; 0044-6033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: 20-HETE and the kidney: resolution of old problems and new beginnings.

    McGiff, J C / Quilley, J

    The American journal of physiology

    1999  Volume 277, Issue 3, Page(s) R607–23

    Abstract: The protean properties of 20-hydroxyeicosatetraenoic acid (HETE), vasoactivity, mitogenicity, and modulation of transport in key nephron segments, serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and ... ...

    Abstract The protean properties of 20-hydroxyeicosatetraenoic acid (HETE), vasoactivity, mitogenicity, and modulation of transport in key nephron segments, serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 and mediator of selective renal effects of ANG II. Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular arterioles, responses that are maintained by 20-HETE inhibition of calcium-activated potassium channels. 20-HETE modulates ion transport in the proximal tubules and the thick ascending limb by affecting the activities of Na+-K+-ATPase and the Na+-K+-2Cl- cotransporter, respectively. The range and diversity of activity of 20-HETE derives in large measure from COX-dependent transformation of 20-HETE to products affecting vasomotion and salt and water excretion. Nitric oxide (NO) exerts a negative modulatory effect on 20-HETE formation; inhibition of NO synthesis produces marked perturbation of renal function resulting from increased 20-HETE production. 20-HETE is an essential component of interactions involving several hormonal systems that have central roles in blood pressure homeostasis, including angiotensins, endothelins, NO, and cytokines. 20-HETE is the preeminent renal eicosanoid, overshadowing PGE2 and PGI2. This review is intended to provide evidence for the physiological roles for cytochrome P-450-derived eicosanoids, particularly 20-HETE, and seeks to extend this knowledge to a conceptual framework for overall cardiovascular function.
    MeSH term(s) Animals ; Carrier Proteins/physiology ; Humans ; Hydroxyeicosatetraenoic Acids/physiology ; Ion Transport ; Kidney/physiology ; Nitric Oxide/physiology ; Renal Circulation/physiology ; Sodium-Potassium-Chloride Symporters ; Sodium-Potassium-Exchanging ATPase/physiology
    Chemical Substances Carrier Proteins ; Hydroxyeicosatetraenoic Acids ; Sodium-Potassium-Chloride Symporters ; Nitric Oxide (31C4KY9ESH) ; 20-hydroxy-5,8,11,14-eicosatetraenoic acid (79551-86-3) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9)
    Language English
    Publishing date 1999
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 2948-8
    ISSN 0002-9513
    ISSN 0002-9513
    DOI 10.1152/ajpregu.1999.277.3.R607
    Database MEDical Literature Analysis and Retrieval System OnLINE

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