5-Lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats

• Published in: Prostaglandins & other lipid mediators 2005, Vol.75 (1), p.91-103
• Main Authors: Hardy, G., Vergnaud, S., Lunardi, J., Peoc’h, M., Bessard, G., Stanke-Labesque, F.
• Format: Article
• Language: English
• Subjects: 5-Lipoxygenase; Animals; aorta; Aorta, Thoracic - enzymology; Aorta, Thoracic - physiopathology; Arachidonate 5-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - metabolism; Arachidonic Acid - pharmacology; Calcimycin - pharmacology; Diabetes; Diabetes Mellitus, Experimental - enzymology; DNA Primers; enzyme activity; experimental diabetes; Gene Expression Regulation, Enzymologic; In Vitro Techniques; Isometric Contraction; Leukotrienes; Leukotrienes - pharmacology; lipoxygenase; Male; Muscle Tonus - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - physiopathology; Rat aorta; Rats; Reverse Transcriptase Polymerase Chain Reaction; Smooth muscle cells
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2004.10.002

We previously reported an activation of the 5-lipoxygenase pathway in aorta from streptozotocin-induced diabetic rats. The aim of this study was to investigate whether this activation was associated with an increased expression of 5-lipoxygenase, an increased cysteinyl leukotriene (CysLT) production in response to arachidonic acid or calcium ionophore A23187 and/or a hypersensitivity of the aorta to CysLTs in streptozotocin-induced diabetic rats. In aorta from diabetic and control rats, reverse transcriptase-PCR and western blot analysis with a specific 5-lipoxygenase antibody provided evidence for the presence of 5-lipoxygenase in aorta. However, the expression of 5-lipoxygenase was not significantly different between diabetic and control rats. Challenge by A23187 (10 μM) and arachidonic acid (10 μM and 0.1 mM) with or without A23187 (10 μmol/l) induced a significant increase of CysLT release (measured by enzyme immunoassay) that was in the same range in aorta from control and diabetic rats. In contrast, aortas from diabetic rats showed a greater sensitivity to LTC 4 and LTD 4 contractile effects. These data suggested that the activation of the 5-lipoxygenase pathway previously reported in streptozotocin-induced diabetic rats could be explained by an augmented sensitivity to CysLTs of the diabetic aorta.