Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress Export

@article{citeulike:2771926, abstract = {We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3-4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-L-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency. 10.1152/ajpheart.00868.2007}, author = {Chen, Yu-Jung and Li, Jing and Quilley, John}, citeulike-article-id = {2771926}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajpheart.00868.2007}, citeulike-linkout-1 = {http://ajpheart.physiology.org/cgi/content/abstract/294/5/H2305}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18326808}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18326808}, day = {1}, doi = {10.1152/ajpheart.00868.2007}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {20-hete}, month = {May}, number = {5}, pages = {H2305--2312}, posted-at = {2008-05-08 15:42:52}, priority = {3}, title = {Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress}, url = {http://dx.doi.org/10.1152/ajpheart.00868.2007}, volume = {294}, year = {2008} }

TY - JOUR ID - citeulike:2771926 L3 - citeulike-article-id:2771926 N2 - We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3-4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-L-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency. 10.1152/ajpheart.00868.2007 IS - 5 JF - Am J Physiol Heart Circ Physiol EP - 2312 TI - Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress VL - 294 SP - H2305 KW - 20-hete AU - Chen, Yu-Jung AU - Li, Jing AU - Quilley, John PY - 2008/05/01/ UR - http://dx.doi.org/10.1152/ajpheart.00868.2007 ER -