Attenuated vascular responsiveness to K+ channel openers in diabetes mellitus: the differential role of reactive oxygen species

作者：Owu Daniel U^*; Orie Nelson N; Nwokocha Chukwuemeka R; Muzyamba Morris; Clapp Lucie H; Osim Eme E

来源：General Physiology and Biophysics, 2013, 32(4): 527-534.

DOI：10.4149/gpb_2013057

• Aorta
• Apocynin
• Diabetes mellitus
• Levcromakalim
• Naringenin
• Superoxide dismutase

The current study examined the responsiveness of blood vessels from diabetic rats to K+ channel openers and explored whether ROS might be involved in any changes. Responses were measured in aortic rings isolated from four weeks streptozotocin (65 mg/kg)-induced diabetic rats. Relaxation to levcromakalim (ATP-sensitive potassium channel K-ATP opener, 10(-9)-10(-5) mol/l) and (+/-)-naringenin (large conductance calcium-activated channel BKca opener, 10(-8)-10(-3) moth) were recorded in phenylephrine (1 mu mol/l) pre-contracted segments in the absence and presence of superoxide dismutase (SOD, 100 mu mol/l) and apocynin (an antioxidant and inhibitor of NADPH oxidase, 100 mu mol/l). Contractions to phenylephrine (10(-9)-10(-5) mol/l) and relaxation to acetylcholine (ACh, 10(-9)-10(-5) mol/l) were also recorded. Relaxation curves for levcromakalim, naringenin and ACh for the diabetic group were shifted to the right (p < 0.05) compared with the control. Contractions to phenylephrine were enhanced in the diabetic group (p < 0.01). SOD restored the ACh response but not those of K+ channel openers. On the other hand, apocynin restored the relaxation to naringenin but had no effect on both levcromalcalim and ACh responses. The results suggest that both K-ATP) and BKCa activities are attenuated in diabetes mellitus and that ROS appears to contribute only to the change in BKCa function.

• 出版日期2013-12