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Signal transduction through Ras‐GTPase and Ca 2+ / calmodulin‐dependent protein kinase II contributes to development of diabetes‐induced renal vascular dysfunction
Author(s) -
Yousif Mariam H. M.
Publication year - 2006
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.1301
Subject(s) - endocrinology , medicine , angiotensin ii , carbachol , sodium nitroprusside , streptozotocin , agonist , diabetes mellitus , nitric oxide , receptor
This study examined the role of Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) and Ras‐GTPase in the development of abnormal reactivity to vasoactive agents in the renal artery of diabetic rats. The vasoconstrictor response induced by norepinephrine (NE), endothelin‐1 (ET‐1) or angiotensin II (Ang II) was significantly increased whereas vasodilator response to carbachol, histamine or sodium nitroprusside (SNP) was not altered in the renal artery segments of the streptozotocin (STZ)‐diabetic rats. Chronic intraperitoneal administration of KN‐93 (5 mg/kg/ alt diem), an inhibitor of CaMKII or FPTIII (1.5 mg/kg/ alt diem), an inhibitor of Ras‐GTPase, produced significant normalization of the altered agonist‐inducedvasoconstrictor responses without affecting blood glucose levels. All the inhibitors were administered for four weeks starting from day one of diabetes induction. Inhibition of Ras‐GTPase or CaMKII did not affect the agonist‐induced vasoconstrictor and vasodilator responses in the non‐diabetic control animals. These data suggest that inhibition of signal transduction involving CaMKII and Ras‐GTPase can prevent development of diabetes‐induced abnormal vascular reactivity in the renal artery. Copyright © 2005 John Wiley & Sons, Ltd.