(Stroke. 1997;28:405-411.)
© 1997 American Heart Association, Inc.
Articles |
High Glucose Concentrations Dilate Cerebral Arteries and Diminish Myogenic Tone Through an Endothelial Mechanism
the Department of Surgery, Division of Vascular Surgery, Oregon Health Sciences University (Portland) (M.J.C., J.M.P.), and the Department of Obstetrics and Gynecology, University of Vermont College of Medicine (G.O.), Burlington, Vt.
Correspondence to Marilyn J. Cipolla, Division of Vascular Surgery, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail cipollam@ohsu.edu.
Background and Purpose Diabetes is associated with cerebrovascular disease and impaired autoregulation of cerebral blood flow. The purpose of this study was to determine the effect of acute glucose exposure on basal tone and myogenic reactivity of isolated rat cerebral arteries.
Methods Posterior cerebral arteries (PCAs, n=38) were dissected from male Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect of elevated glucose on cerebral endothelial modulation of basal tone was determined by mechanical denudation and the use of inhibitors of both nitric oxide and prostaglandin synthesis.
Results Arteries exposed to 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2±1% versus 28±2%; P<.01) and responded passively to increases in TMP. Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44 mmol/L glucose, which decreased tone from 30±5% to 5±4% (P<.01). Glucose-induced dilations were concentration dependent such that half-maximal responses were obtained at 25±2 mmol/L. Endothelial removal abolished this effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 46±6% versus 49±5%; P>.05), as did inhibition of nitric oxide production with 0.3 mmol/L nitro-L-arginine (percent tone, 52±4% versus 46±3%; P>.05); however, blockade of the cyclooxygenase pathway with indomethacin (10-5 mmol/L) only partially inhibited the dilation to glucose (percent tone, 32±3% in 5.5 mmol/L versus 12.4±3% in 44 mmol/L; P<.01).
Conclusions Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism that involves nitric oxide and prostaglandins.
Editorial Comment
Department of Physiology and BiophysicsUniversity of Nebraska Medical CenterOmaha, Neb
This article has been cited by other articles:
 |
|
 |
|
  Y.-S. Kim, R. Krogh-Madsen, P. Rasmussen, P. Plomgaard, S. Ogoh, N. H. Secher, and J. J. van Lieshout Effects of hyperglycemia on the cerebrovascular response to rhythmic handgrip exercise Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H467 - H473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. J. Lott, C. Hogeman, M. Herr, R. Gabbay, and L. I. Sinoway Effects of an oral glucose tolerance test on the myogenic response in healthy individuals Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H304 - H310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lavi, D. Gaitini, V. Milloul, and G. Jacob Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1856 - H1861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Maneen, R. Hannah, L. Vitullo, N. DeLance, and M. J. Cipolla Peroxynitrite Diminishes Myogenic Activity and Is Associated With Decreased Vascular Smooth Muscle F-Actin in Rat Posterior Cerebral Arteries Stroke, March 1, 2006; 37(3): 894 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ito, Y. P. R. Jarajapu, D. L. Guberski, M. B. Grant, and H. J. Knot Myogenic Tone and Reactivity of Rat Ophthalmic Artery in Acute Exposure to High Glucose and in a Type II Diabetic Model Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 683 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Bagi, E. Toth, A. Koller, and G. Kaley Microvascular dysfunction after transient high glucose is caused by superoxide-dependent reduction in the bioavailability of NO and BH4 Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H626 - H633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Flores, S. Rojas, C. Aguayo, J. Parodi, G. Mann, J. D. Pearson, P. Casanello, and L. Sobrevia Rapid Stimulation of L-Arginine Transport by D-Glucose Involves p42/44mapk and Nitric Oxide in Human Umbilical Vein Endothelium Circ. Res., January 10, 2003; 92(1): 64 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Frisbee, K. G. Maier, and D. W. Stepp Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2160 - H2168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. Davidge Prostaglandin H Synthase and Vascular Function Circ. Res., October 12, 2001; 89(8): 650 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Cipolla, N. Lessov, E. S. Hammer, and A. B. Curry Threshold Duration of Ischemia for Myogenic Tone in Middle Cerebral Arteries : Effect on Vascular Smooth Muscle Actin Stroke, July 1, 2001; 32(7): 1658 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Calles-Escandon and M. Cipolla Diabetes and Endothelial Dysfunction: A Clinical Perspective Endocr. Rev., February 1, 2001; 22(1): 36 - 52. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Komers, J. N. Lindsley, T. T. Oyama, K. M. Allison, and S. Anderson Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes Am J Physiol Renal Physiol, September 1, 2000; 279(3): F573 - F583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Pieper Review of Alterations in Endothelial Nitric Oxide Production in Diabetes : Protective Role of Arginine on Endothelial Dysfunction Hypertension, May 1, 1998; 31(5): 1047 - 1060. [Full Text] [PDF]
|
|