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PPARγ Dependence Of the Cyclosporine‐Isoprenaline Renovascular Interaction: Roles of Nitric Oxide Synthase And Heme Oxygenase
Author(s) -
AbdElrahman Khaled Soliman,
ElGowelli Hanan M,
Saad Evan I,
AbdelGalil AbdelGalil A,
ElMas Mahmoud M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1087.8
Subject(s) - heme oxygenase , nitric oxide synthase , chemistry , heme , isoprenaline , nitric oxide , oxygenase , atp synthase , pharmacology , biochemistry , medicine , enzyme , organic chemistry , stimulation
Cyclosporine (CSA) impairs renal vasodilations caused by β‐adrenoceptor activation. The hypothesis was tested that the CSA‐isoprenaline renal interaction is modulated by PPARγ and related NOS/HO signaling. Renal vasodilations caused by bolus isoprenaline (1 μmol) in phenylephrine‐preconstricted perfused kidneys of rats was reduced after prior infusion of zinc protoporphyrin IX (ZnPP, HO inhibitor) or GW9662 (PPARγ antagonist) but not L‐NAME (NOS inhibitor), suggesting the involvement of PPARγ and HO‐derived CO in the isoprenaline response. CSA (5 μM) significantly attenuated isoprenaline vasodilations and this effect was abolished in presence of GW9662 but not L‐NAME or ZnPP. Also, treatment with the PPARγ agonist pioglitazone or with L‐arginine or hemin, substrates for NOS and HO, respectively, eliminated CSA‐evoked reduction in isoprenaline responses. The protection conferred by pioglitazone against CSA‐isoprenaline interaction was maintained in L‐NAME‐treated kidneys and disappeared after treatment with ZnPP or GW9662. In conclusion, the activation of the PPARγ/HO/CO cascade is probably the cellular mechanism that underlies the beneficial effect of pioglitazone on the CSA‐isoprenaline interaction. Moreover, facilitation of NOS/NO or HO/CO signaling offsets the harmful effect of CSA on isoprenaline vasodilation.