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  1. Book ; Thesis: Imatinib relaxes the pulmonary venous bed of guinea pigs

    Maihöfer, Nina Andrea

    2017  

    Author's details vorgelegt von Nina Andrea Maihöfer
    Language English
    Size 13, [1] Seiten, Illustrationen
    Publishing place Aachen
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2017
    Note Die Dissertation wurde zuvor 2017 als Aufsatz in der Zeitschrift "Respiratory research" (2017,18:32) veröffentlicht; DOI 10.1186/s12931-017-0514-0
    HBZ-ID HT019549021
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Imatinib relaxes the pulmonary venous bed of guinea pigs.

    Maihöfer, Nina A / Suleiman, Said / Dreymüller, Daniela / Manley, Paul W / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian / Rieg, Annette D

    Respiratory research

    2017  Volume 18, Issue 1, Page(s) 32

    Abstract: Background: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)- ... ...

    Abstract Background: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)-receptor (PDGFR), acts antiproliferative and relaxes pulmonary arteries. However so far, the relaxant effects of imatinib on pulmonary veins (PVs) and on the postcapillary resistance are unknown, although pulmonary hypertension (PH) due to left heart disease (LHD) is most common and primarily affects PVs. Next, it is unknown whether activation of PDGFR alters the pulmonary venous tone. Due to the reported adverse effects of systemic imatinib, we evaluated the effects of nebulized imatinib on the postcapillary resistance.
    Methods: Precision-cut lung slices (PCLS) were prepared from guinea pigs. PVs were pre-constricted with Endothelin-1 (ET-1) and the imatinib-induced relaxation was studied by videomicroscopy; PDGF-BB-related vascular properties were evaluated as well. The effects of perfused/nebulized imatinib on the postcapillary resistance were studied in cavine isolated perfused lungs (IPL). Intracellular cAMP/cGMP was measured by ELISA in PVs.
    Results: In PCLS, imatinib (100 μM) relaxed pre-constricted PVs (126%). In PVs, imatinib increased cAMP, but not cGMP and inhibition of adenyl cyclase or protein kinase A reduced the imatinib-induced relaxation. Further, inhibition of K
    Conclusions: Imatinib-induced relaxation depends on cAMP and on the activation of K
    Language English
    Publishing date 2017-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-9921
    ISSN (online) 1465-993X
    ISSN 1465-9921
    DOI 10.1186/s12931-017-0514-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Erratum to: Imatinib relaxes the pulmonary venous bed of guinea pigs.

    Maihöfer, Nina A / Suleiman, Said / Dreymüller, Daniela / Manley, Paul W / Rossaint, Rolf / Uhlig, Stefan / Martin, Christian / Rieg, Annette D

    Respiratory research

    2017  Volume 18, Issue 1, Page(s) 121

    Language English
    Publishing date 2017--19
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-9921
    ISSN (online) 1465-993X
    ISSN 1465-9921
    DOI 10.1186/s12931-017-0612-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Levosimendan Relaxes Pulmonary Arteries and Veins in Precision-Cut Lung Slices - The Role of KATP-Channels, cAMP and cGMP.

    Rieg, Annette D / Rossaint, Rolf / Verjans, Eva / Maihöfer, Nina A / Uhlig, Stefan / Martin, Christian

    PloS one

    2013  Volume 8, Issue 6, Page(s) e66195

    Abstract: Introduction: Levosimendan is approved for left heart failure and is also used in right heart failure to reduce right ventricular afterload. Despite the fact that pulmonary arteries (PAs) and pulmonary veins (PVs) contribute to cardiac load, their ... ...

    Abstract Introduction: Levosimendan is approved for left heart failure and is also used in right heart failure to reduce right ventricular afterload. Despite the fact that pulmonary arteries (PAs) and pulmonary veins (PVs) contribute to cardiac load, their responses to levosimendan are largely unknown.
    Materials and methods: Levosimendan-induced vasorelaxation of PAs and PVs was studied in precision-cut lung slices from guinea pigs by videomicroscopy; baseline luminal area was defined as 100%. Intracellular cAMP- and cGMP-levels were measured by ELISA and NO end products were determined by the Griess reaction.
    Results: Levosimendan relaxed control PVs (116%) and those pre-constricted with an endothelinA-receptor agonist (119%). PAs were only relaxed if pre-constricted (115%). Inhibition of KATP-channels (glibenclamide), adenyl cyclase (SQ 22536) and protein kinase G (KT 5823) largely attenuated the levosimendan-induced relaxation in control PVs, as well as in pre-constricted PAs and PVs. Inhibition of BKCa (2+)-channels (iberiotoxin) and Kv-channels (4-aminopyridine) only contributed to the relaxant effect of levosimendan in pre-constricted PAs. In both PAs and PVs, levosimendan increased intracellular cAMP- and cGMP-levels, whereas NO end products remained unchanged. Notably, basal NO-levels were higher in PVs. The KATP-channel activator levcromakalim relaxed PAs dependent on cAMP/PKA/PKG and increased cAMP-levels in PAs.
    Discussion: Levosimendan initiates complex and divergent signaling pathways in PAs and PVs. Levosimendan relaxes PAs and PVs primarily via KATP-channels and cAMP/cGMP; in PAs, BKCa (2+)- and Kv-channels are also involved. Our findings with levcromakalim do further suggest that in PAs the activation of KATP-channels leads to the production of cAMP/PKA/PKG. In conclusion, these results suggest that levosimendan might reduce right ventricular afterload by relaxation of PAs as well as pulmonary hydrostatic pressure and pulmonary edema by relaxation of PVs.
    MeSH term(s) Animals ; Culture Media ; Cyclic AMP/physiology ; Cyclic GMP/physiology ; Female ; Guinea Pigs ; Hydrazones/pharmacology ; KATP Channels/physiology ; Lung/blood supply ; Pulmonary Artery/drug effects ; Pulmonary Artery/physiology ; Pyridazines/pharmacology ; Simendan ; Vasodilation/drug effects
    Chemical Substances Culture Media ; Hydrazones ; KATP Channels ; Pyridazines ; Simendan (349552KRHK) ; Cyclic AMP (E0399OZS9N) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2013-06-18
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0066195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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