on June 3, 2002
Published online before print June 3, 2002, doi: 10.1161/01.HYP.0000022806.87281.62
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 30, 2002
From the Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC. * To whom correspondence should be addressed. E-mail: amiller{at}wfubmc.edu.
Abstract—Although insulin-mediated vasodilation is impaired in insulin resistance, the mechanisms of this are unknown. We investigated factors mediating vasoactive responses to insulin in control and insulin-resistant rats. Responses to insulin in small mesenteric arteries from control and insulin-resistant rats were investigated after blocking endothelin-A receptors, cyclooxygenase, nitric oxide synthase, and potassium channels. In addition, insulin's effect on prostacyclin production in small mesenteric blood vessels was assessed by enzyme immunoassay. Insulin induced a concentration-dependent vasodilation in control arteries that was absent in arteries from insulin-resistant rats. However, in the presence of BQ610, an endothelin-A receptor antagonist, the response to insulin was normalized in insulin-resistant arteries. In control arteries, insulin-induced vasodilation was completely inhibited by indomethacin, meclofenamate, glibenclamide, or potassium chloride. In contrast, neither n-nitro-L-arginine nor the combination of charybdotoxin and apamin altered vasodilation to insulin. In insulin-resistant arteries in the presence of BQ610, vasodilation was also inhibited by indomethacin, glibenclamide, and potassium chloride. Insulin increased prostacyclin production in small mesenteric blood vessels from both groups of rats to a similar degree. Insulin-induced vasodilation in small rat mesenteric arteries is mediated through prostacyclin- and ATP-dependent potassium channels. However, insulin-resistant arteries do not vasodilate to insulin unless endothelin-A receptors are blocked. Thus, impaired relaxation to insulin in insulin-resistant rats is due to enhanced vasoconstriction by endothelin, which offsets a normal vasodilatory response to insulin.
Revised on February 19, 2002
Enhanced Endothelin Activity Prevents Vasodilation to Insulin in Insulin Resistance
Allison W. Miller*;
Key words: insulin resistance • endothelin • prostacyclin • potassium channels • insulin
This article has been cited by other articles:
 |
|
 |
|
  J. Steinberger, S. R. Daniels, R. H. Eckel, L. Hayman, R. H. Lustig, B. McCrindle, and M. L. Mietus-Snyder Progress and Challenges in Metabolic Syndrome in Children and Adolescents: A Scientific Statement From the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism Circulation, February 3, 2009; 119(4): 628 - 647. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sachidanandam, J. R. Hutchinson, M. M. Elgebaly, E. M. Mezzetti, M.-H. Wang, and A. Ergul Differential Effects of Diet-Induced Dyslipidemia and Hyperglycemia on Mesenteric Resistance Artery Structure and Function in Type 2 Diabetes J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Lteif, A. D. Fulford, R. V. Considine, I. Gelfand, A. D. Baron, and K. J. Mather Hyperinsulinemia fails to augment ET-1 action in the skeletal muscle vascular bed in vivo in humans Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1510 - E1517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dhaun, J. Goddard, D. E. Kohan, D. M. Pollock, E. L. Schiffrin, and D. J. Webb Role of Endothelin-1 in Clinical Hypertension: 20 Years On Hypertension, September 1, 2008; 52(3): 452 - 459. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sachidanandam, M. M. Elgebaly, A. K. Harris, J. R. Hutchinson, E. M. Mezzetti, V. Portik-Dobos, and A. Ergul Effect of chronic and selective endothelin receptor antagonism on microvascular function in Type 2 diabetes Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2743 - H2749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Eringa, C. D. A. Stehouwer, M. H. Roos, N. Westerhof, and P. Sipkema Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1134 - E1139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Sarafidis and G. L. Bakris Insulin and Endothelin: An Interplay Contributing to Hypertension Development? J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 379 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kobayashi, T. Matsumoto, and K. Kamata IGF-I-induced enhancement of contractile response in organ-cultured aortae from diabetic rats is mediated by sustained thromboxane A2 release from endothelial cells J. Endocrinol., August 1, 2005; 186(2): 367 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Srinivasan, P. Herrero, J. B. McGill, J. Bennik, B. Heere, D. Lesniak, V. G. Davila-Roman, and R. J. Gropler The Effects of Plasma Insulin and Glucose on Myocardial Blood Flow in Patients With Type 1 Diabetes Mellitus J. Am. Coll. Cardiol., July 5, 2005; 46(1): 42 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. G. Katakam, C. D. Tulbert, J. A. Snipes, B. Erdos, A. W. Miller, and D. W. Busija Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H854 - H860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Juan, Y.-W. Shen, Y. Chien, Y.-J. Lin, S.-F. Chang, and L.-T. Ho Insulin infusion induces endothelin-1-dependent hypertension in rats Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E948 - E954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verma, A. W. Miller, and D. W. Busija Endothelin Antagonism and Insulin's Vascular Effects * Response: Endothelin Antagonism and Insulin's Vascular Effects Hypertension, December 1, 2002; 40 (6): e12 - e13. [Full Text] [PDF]
|
|