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The causal role of PKC in Reduced Endothelial Ca 2+ Signaling and Impaired EDHF‐Mediated Uterine Vasodilation in Diabetic Pregnancy
Author(s) -
Gokitalia I,
Linder Erika
Publication year - 2012
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.26.1_supplement.1056.8
Subject(s) - vasodilation , protein kinase c , endocrinology , medicine , diabetes mellitus , endothelium , vasoconstriction , endothelial dysfunction , pharmacology , signal transduction , chemistry , biochemistry
Increased PKC activity is an essential mechanism of diabetic vascular complications. To characterize the role of PKC in uterine vascular dysfunction during diabetic pregnancy we: (1) defined the effects of PKC activation (PDBu) or inhibition (bisindolylmaleimide, BIS) on EDHF‐mediated responses to ACh; (2) elucidated PKC dependence of ACh‐induced endothelial cell (EC) [Ca 2+ ] i . Diabetes was induced by streptozotocin (STZ) injection. ACh was tested in uterine arteries from control and diabetic pregnant rats in the presence of L‐NNA and indomethacin. Fura‐2 based SMC or EC [Ca 2+ ] i responses were studied as well. Diabetes reduced EDHF‐mediated vasodilation from 90 ± 4 % to 26 ± 9 % at 10 μM ACh. SMC and EC [Ca 2+ ] i responses were markedly reduced as well. PDBu inhibited ACh‐evoked vasodilation (14 ± 5 %) and associated SMC [Ca 2+ ] i responses of control vessels. BIS partially restored EDHF‐mediated vasodilation (to 72 ± 10 %) and SMC [Ca 2+ ] i in diabetic vessels. PDBu reduced EC [Ca 2+ ] i responses of control vessels to ACh by 50 ± 7 %. BIS significantly restored EC [Ca 2+ ] i elevations to ACh in diabetic arteries. PKC‐dependent reduction in EC Ca 2+ signaling underlies impaired EDHF‐mediated uterine vasodilation during diabetic pregnancy. Inhibition of PKC may serve as a therapeutic strategy to improve uterine vasodilation in pregnancies complicated with diabetes. Supported by NIH HL088245