| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Pharmacology and Human Physiology, University of Bari Medical School, Bari, Italy; and 2Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland
Submitted 31 January 2005 ; accepted in final form 18 March 2005
Insulin stimulates production of NO in vascular endothelium via activation of phosphatidylinositol (PI) 3-kinase, Akt, and endothelial NO synthase. We hypothesized that insulin resistance may cause imbalance between endothelial vasodilators and vasoconstrictors (e.g., NO and ET-1), leading to hypertension. Twelve-week-old male spontaneously hypertensive rats (SHR) were hypertensive and insulin resistant compared with control Wistar-Kyoto (WKY) rats (systolic blood pressure 202 ± 11 vs. 132 ± 10 mmHg; fasting plasma insulin 5 ± 1 vs. 0.9 ± 0.1 ng/ml; P < 0.001). In WKY rats, insulin stimulated dose-dependent relaxation of mesenteric arteries precontracted with norepinephrine (NE) ex vivo. This depended on intact endothelium and was blocked by genistein, wortmannin, or N
-nitro-L-arginine methyl ester (inhibitors of tyrosine kinase, PI3-kinase, and NO synthases, respectively). Vasodilation in response to insulin (but not ACh) was impaired by 20% in SHR (vs. WKY, P < 0.005). Preincubation of arteries with insulin significantly reduced the contractile effect of NE by 20% in WKY but not SHR rats. In SHR, the effect of insulin to reduce NE-mediated vasoconstriction became evident when insulin pretreatment was accompanied by ET-1 receptor blockade (BQ-123, BQ-788). Similar results were observed during treatment with the MEK inhibitor PD-98059. In addition, insulin-stimulated secretion of ET-1 from primary endothelial cells was significantly reduced by pretreatment of cells with PD-98059 (but not wortmannin). We conclude that insulin resistance in SHR is accompanied by endothelial dysfunction in mesenteric vessels with impaired PI3-kinase-dependent NO production and enhanced MAPK-dependent ET-1 secretion. These results may reflect pathophysiology in other vascular beds that directly contribute to elevated peripheral vascular resistance and hypertension.
hypertension; endothelin-1; nitric oxide
This article has been cited by other articles:
|
|
 |
|
  M. A. Potenza, F. Addabbo, and M. Montagnani Vascular actions of insulin with implications for endothelial dysfunction Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E568 - E577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Potenza, S. Gagliardi, L. De Benedictis, A. Zigrino, E. Tiravanti, G. Colantuono, A. Federici, L. Lorusso, V. Benagiano, M. J. Quon, et al. Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E685 - E694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q.-J. Zhang, S. L. McMillin, J. M. Tanner, M. Palionyte, E. D. Abel, and J. D. Symons Endothelial nitric oxide synthase phosphorylation in treadmill-running mice: role of vascular signalling kinases J. Physiol., August 1, 2009; 587(15): 3911 - 3920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto, K. Ishida, N. Nakayama, T. Kobayashi, and K. Kamata Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1388 - H1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lee, T. Palaia, and L. Ragolia Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation Am J Physiol Cell Physiol, February 1, 2009; 296(2): C327 - C338. [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]
|
|
|
|
|
|
J. Cacho, J. Sevillano, J. de Castro, E. Herrera, and M. P. Ramos Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1269 - E1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Davis, M. Jenab, J. P. Vanden Heuvel, T. Furlong, and S. Taylor Tree Nut and Peanut Consumption in Relation to Chronic and Metabolic Diseases Including Allergy J. Nutr., September 1, 2008; 138(9): 1757S - 1762S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bertrand, S. Horman, C. Beauloye, and J.-L. Vanoverschelde Insulin signalling in the heart Cardiovasc Res, July 15, 2008; 79(2): 238 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Lee, S. Xia, and L. Ragolia Upregulation of AT2 receptor and iNOS impairs angiotensin II-induced contraction without endothelium influence in young normotensive diabetic rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R144 - R154. [Abstract] [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]
|
|
|
|
 |
|
 W. Bakker, P. Sipkema, C. D.A. Stehouwer, E. H. Serne, Y. M. Smulders, V. W.M. van Hinsbergh, and E. C. Eringa Protein Kinase C {theta} Activation Induces Insulin-Mediated Constriction of Muscle Resistance Arteries Diabetes, March 1, 2008; 57(3): 706 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Jonk, A. J. H. M. Houben, R. T. de Jongh, E. H. Serne, N. C. Schaper, and C. D. A. Stehouwer Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension Physiology, August 1, 2007; 22(4): 252 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Serne, R. T. de Jongh, E. C. Eringa, R. G. IJzerman, and C. D.A. Stehouwer Microvascular Dysfunction: A Potential Pathophysiological Role in the Metabolic Syndrome Hypertension, July 1, 2007; 50(1): 204 - 211. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Potenza, F. L. Marasciulo, M. Tarquinio, E. Tiravanti, G. Colantuono, A. Federici, J.-a Kim, M. J. Quon, and M. Montagnani EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1378 - E1387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Bradley, M. G. Clark, and S. Rattigan Acute effects of wortmannin on insulin's hemodynamic and metabolic actions in vivo Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E779 - E787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iantorno, H. Chen, J.-a Kim, M. Tesauro, D. Lauro, C. Cardillo, and M. J. Quon Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E756 - E764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Potenza, F. L. Marasciulo, M. Tarquinio, M. J. Quon, and M. Montagnani Treatment of Spontaneously Hypertensive Rats With Rosiglitazone and/or Enalapril Restores Balance Between Vasodilator and Vasoconstrictor Actions of Insulin With Simultaneous Improvement in Hypertension and Insulin Resistance Diabetes, December 1, 2006; 55(12): 3594 - 3603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Harris, S. R. Bailey, J. Elliott, and A. Longland Countermeasures for Pasture-Associated Laminitis in Ponies and Horses J. Nutr., July 1, 2006; 136(7): 2114S - 2121S. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
