Premium
Phosphoinositide 3‐kinase contributes to diabetes‐induced abnormal vascular reactivity in rat perfused mesenteric bed
Author(s) -
Yousif Mariam H. M.
Publication year - 2008
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1463
Subject(s) - endocrinology , medicine , vascular smooth muscle , diabetes mellitus , vasodilation , pi3k/akt/mtor pathway , mesenteric arteries , phosphatidylinositol , angiotensin ii , endothelin receptor , chemistry , kinase , signal transduction , blood pressure , artery , receptor , biochemistry , smooth muscle
Phosphatidylinositol 3‐kinase (PI3K) is a signaling enzyme that plays key roles in vascular growth, proliferation, and cellular apoptosis and is implicated in modulating vascular smooth muscle contractility. The aim of this study was to determine whether PI3K contributes to development of diabetes‐induced abnormal vascular reactivity to selected vasoactive agonists. The effect of 2‐(4‐morpholinyl)‐8‐phenyl‐4H‐1‐benzopyran‐4‐one (LY294002), a selective PI3K inhibitor, on isolated perfused mesenteric vascular bed from streptozotocin (STZ)‐diabetic rats was investigated. Changes in perfusion pressure, which reflected peripheral resistance, were measured using isolated perfused mesenteric vascular beds. Our results showed that STZ treatment produced an increase in the vasoconstrictor response to norepinephrine (NE), angiotensin II (Ang II) and endothelin‐1 (ET‐1), and an attenuated vasodilator response to carbachol and histamine in the isolated perfused mesenteric vascular bed from STZ‐diabetic animals. Chronic inhibition of PI3K with LY294002 resulted in prevention of diabetes‐induced abnormal vascular reactivity to the vasoactive agonists. However, the high blood glucose levels were not normalized. Results of this study indicate that selective inhibition of PI3K can attenuate the development of diabetes‐induced abnormal vascular responsiveness in the isolated perfused mesenteric vascular bed. Copyright © 2008 John Wiley & Sons, Ltd.