on February 19, 2004
Published online before print February 19, 2004, doi: 10.1161/01.STR.0000119753.05670.F1
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 10, 2003
From the Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC (B.E., S.A.S., J.A.S., A.W.M., D.W.B.), and Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary (B.E.). * To whom correspondence should be addressed. E-mail: berdos{at}wfubmc.edu.
Background and Purpose--Insulin resistance (IR) increases the risk of stroke in humans. One possible underlying factor is cerebrovascular dysfunction resulting from altered K+ channel function. Thus, the goal of this study was to examine K+ channel-mediated relaxation in IR cerebral arteries. Methods--Experiments were performed on pressurized isolated middle cerebral arteries (MCAs) from fructose-fed IR and control rats. Results--Dilator responses to iloprost, which are BKCa channel mediated, were reduced in the IR compared with control arteries (19±2% versus 33±2% at 10-6 mol/L). Similarly, relaxation to the KATP opener pinacidil was diminished in the IR MCAs (17±2%) compared with controls (38±2% at 10-5 mol/L). IR also reduced the KATP channel-dependent component in calcitonin gene-related peptide-induced dilation; however, the magnitude of the relaxation remained unchanged in IR because of a nonspecified K+ channel-mediated compensatory mechanism. In contrast, Kir channel-mediated relaxation elicited by increases in extracellular [K+] (4 to 12 mmol/L) was similar in the control and IR arteries. Blockade of the Kir and Kv channels with Ba2+ and 4-aminopyridine, respectively, constricted the MCAs in both experimental groups with no significant difference. Pretreatment of arteries with superoxide dismutase (200 U/mL) plus catalase (150 U/mL) restored the dilatory responses to iloprost and pinacidil in the IR arteries. Immunoblots showed that the expressions of the pore-forming subunits of the examined K+ channels are not altered by IR. Conclusions--IR induces a type-specific K+ channel dysfunction mediated by reactive oxygen species. The alteration of KATP and BKCa channel-dependent vascular responses may be responsible for the increased risk of cerebrovascular events in IR.
Accepted on December 15, 2003
Potassium Channel Dysfunction in Cerebral Arteries of Insulin-Resistant Rats Is Mediated by Reactive Oxygen Species
Benedek Erdös MD*;
Key words: diabetes mellitus • insulin resistance • middle cerebral artery • potassium channels • oxidative stress • rats
This article has been cited by other articles:
 |
|
 |
|
  S. Koba, Z. Gao, and L. I. Sinoway Oxidative stress and the muscle reflex in heart failure J. Physiol., November 1, 2009; 587(21): 5227 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nadeem, D. S. Ponnoth, H. R. Ansari, T. P. Batchelor, R. D. Dey, C. Ledent, and S. J. Mustafa A2A Adenosine Receptor Deficiency Leads to Impaired Tracheal Relaxation via NADPH Oxidase Pathway in Allergic Mice J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. V. G. Katakam, F. Domoki, J. A. Snipes, A. R. Busija, Y. P. R. Jarajapu, and D. W. Busija Impaired mitochondria-dependent vasodilation in cerebral arteries of Zucker obese rats with insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R289 - R298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kinoshita, N. Matsuda, H. Kaba, N. Hatakeyama, T. Azma, K. Nakahata, Y. Kuroda, K. Tange, H. Iranami, and Y. Hatano Roles of Phosphatidylinositol 3-Kinase-Akt and NADPH Oxidase in Adenosine 5'-Triphosphate-Sensitive K+ Channel Function Impaired by High Glucose in the Human Artery Hypertension, September 1, 2008; 52(3): 507 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Harris, M. M. Elgebaly, W. Li, K. Sachidanandam, and A. Ergul Effect of chronic endothelin receptor antagonism on cerebrovascular function in type 2 diabetes Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1213 - R1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Erdei, Z. Bagi, I. Edes, G. Kaley, and A. Koller H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H649 - H656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, W. F. Jackson, G. D. Fink, and J. J. Galligan Activation of Potassium Channels by Tempol in Arterial Smooth Muscle Cells From Normotensive and Deoxycorticosterone Acetate-Salt Hypertensive Rats Hypertension, December 1, 2006; 48(6): 1080 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhou, X.-L. Wang, K. G. Lamping, and H.-C. Lee Inhibition of Protein Kinase Cbeta Protects against Diabetes-Induced Impairment in Arachidonic Acid Dilation of Small Coronary Arteries J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 199 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Lyle and K. K. Griendling Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology, August 1, 2006; 21: 269 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kinoshita, T. Azma, H. Iranami, K. Nakahata, Y. Kimoto, M. Dojo, O. Yuge, and Y. Hatano Synthetic Peroxisome Proliferator-Activated Receptor-{gamma} Agonists Restore Impaired Vasorelaxation via ATP-Sensitive K+ Channels by High Glucose J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 312 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Burnham, I. T. Johnson, and A. H. Weston Reduced Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels from arteries of Type 2 diabetic Zucker diabetic fatty rats Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1520 - H1527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Erdos, J. A. Snipes, C. D. Tulbert, P. Katakam, A. W. Miller, and D. W. Busija Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1264 - H1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, X. Bian, S. W. Watts, and A. Hlavacova Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats Hypertension, November 1, 2005; 46(5): 1154 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D'Angelo, A. A. Elmarakby, D. M. Pollock, and D. W. Stepp Fructose Feeding Increases Insulin Resistance but Not Blood Pressure in Sprague-Dawley Rats Hypertension, October 1, 2005; 46(4): 806 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Oltman, L. J. Coppey, J. S. Gellett, E. P. Davidson, D. D. Lund, and M. A. Yorek Progression of vascular and neural dysfunction in sciatic nerves of Zucker diabetic fatty and Zucker rats Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E113 - E122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Gutterman, H. Miura, and Y. Liu Redox Modulation of Vascular Tone: Focus of Potassium Channel Mechanisms of Dilation Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 671 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Faraci Oxidative Stress: The Curse That Underlies Cerebral Vascular Dysfunction? Stroke, February 1, 2005; 36(2): 186 - 188. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Phillips, F. A. Sylvester, and J. C. Frisbee Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R522 - R530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Erdos, J. A. Snipes, B. Kis, A. W. Miller, and D. W. Busija Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1456 - R1461. [Abstract] [Full Text] [PDF]
|
|