Attenuated vascular responsiveness to K+ channel openers in diabetes mellitus: the differential role of reactive oxygen species.
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 KATP opener, 10(-9)-10(-5) mol/l) and (+/-)-naringenin (large conductance calcium-activated channel BKCa opener, 10(-8)-10(-3) mol/l) were recorded in phenylephrine (1 µmol/l) pre-contracted segments in the absence and presence of superoxide dismutase (SOD, 100 µmol/l) and apocynin (an antioxidant and inhibitor of NADPH oxidase, 100 µmol/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 levcromakalim and ACh responses. The results suggest that both KATP and BKCa activities are attenuated in diabetes mellitus and that ROS appears to contribute only to the change in BKCa function.
Department of Physiology, College of Medical Sciences, University of Calabar, Calabar, Nigeria. danielowu@unical.edu.ng.
Daniel U
DU
Owu
Nelson N
NN
Orie
Chukwuemeka R
CR
Nwokocha
Morris
M
Muzyamba
Lucie H
LH
Clapp
Eme E
EE
Osim
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D044950:Flavanones / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000098:Acetophenones; D001786:Blood Glucose; D044950:Flavanones; D016166:Free Radical Scavengers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D019806:Cromakalim; D010656:Phenylephrine; C056165:acetovanillone; D013482:Superoxide Dismutase; C005273:naringenin; D000109:Acetylcholine