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Horm Metab Res 2005; 37: 56-60
DOI: 10.1055/s-2005-861370
Review
© Georg Thieme Verlag KG Stuttgart · New York

Functional Abnormalities in Isolated Arteries from Goto-Kakizaki and Streptozotocin-treated Diabetic Rat Models

E.  Brøndum1 , H.  Nilsson1 , C.  Aalkjær1
  • 1 The Water and Salt Research Center, Institute of Physiology and Biophysics, University of Aarhus, Denmark
Further Information

Publication History

Received 15 December 2004

Accepted after Revision 2 February 2005

Publication Date:
25 May 2005 (online)

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Abstract

Several different rat models have been developed for both type 1 and type 2 diabetes with the aim of displaying specific traits of diabetes. For example, a review on nephropathy associated with type 2 diabetes included 16 different rodent models [1]; new models are still being developed. The large number of different models developed for different traits makes it difficult to choose the right model for a given study. It is often a problem that the models are not sufficiently characterized, which makes it easy to misinterpret data or even come to the wrong conclusions.
In this brief review, we will concentrate on the functional responses obtained in vitro from mesenteric arteries and aortic segments from rat models of diabetes. Since it is beyond the scope of this review to overview all different rodent models of diabetes, we will focus on two commonly used models of diabetes, namely the streptozotocin (STZ)-induced type 1 diabetic rat model and the inbred type 2 diabetic Goto-Kakizaki (GK)-rat model.

Key words

Diabetes mellitus - Rat - Goto-Kakizaki - Streptozotocin

References

  • 1 Janssen U, Phillips A O, Floege J. Rodent models of nephropathy associated with type II diabetes.  J Nephrol. 1999;  12 (3) 159-172
    PubMedGoogle Scholar
  • 2 Skrha J. Pathogenesis of angiopathy in diabetes.  Acta Diabetol. 2003;  40 Suppl 2 S324-S329
    CrossrefPubMedGoogle Scholar
  • 3 King G L, Shiba T, Oliver J, Inoguchi T, Bursell S E. Cellular and molecular abnormalities in the vascular endothelium of diabetes mellitus.  Annu Rev Med. 1994;  45 179-188
    CrossrefPubMedGoogle Scholar
  • 4 Mulvany M J, Aalkjaer C. Structure and function of small arteries.  Physiol Rev. 1990;  70 (4) 921-961
    PubMedGoogle Scholar
  • 5 Martin B C, Warram J H, Krolewski A S, Bergman R N, Soeldner J S, Kahn C R. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study.  Lancet. 1992;  340 (8825) 925-929
    CrossrefPubMedGoogle Scholar
  • 6 Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas.  Physiol Res. 2001;  50 (6) 537-546
    PubMedGoogle Scholar
  • 7 Abebe W, Harris K H, MacLeod K M. Enhanced contractile responses of arteries from diabetic rats to alpha 1-adrenoceptor stimulation in the absence and presence of extracellular calcium.  J Cardiovasc Pharmacol. 1990;  16 (2) 239-248
    PubMedGoogle Scholar
  • 8 Abebe W, MacLeod K M. Enhanced arterial contractility to noradrenaline in diabetic rats is associated with increased phosphoinositide metabolism.  Can J Physiol Pharmacol. 1991;  69 (3) 355-361
    PubMedGoogle Scholar
  • 9 Wong K K. A significant increase of aortic response to a combination of norepinephrine and KCl in aorta isolated from 2-month diabetic rats induced by streptozocin.  Artery. 1996;  22 (3) 164-171
    PubMedGoogle Scholar
  • 10 Nobe K, Sakai Y, Maruyama Y, Momose K. Hyper-reactivity of diacylglycerol kinase is involved in the dysfunction of aortic smooth muscle contractility in streptozotocin-induced diabetic rats.  Br J Pharmacol. 2002;  136 (3) 441-451
    CrossrefPubMedGoogle Scholar
  • 11 Mahmoudian M, Behnaz F, Rezaei E. Diabetes-induced changes in the contractility of the aorta and pA2 of nifedipine in the rat.  Acta Diabetol. 1996;  33 (2) 114-117
    PubMedGoogle Scholar
  • 12 Kobayashi T, Kamata K. Effect of insulin treatment on smooth muscle contractility and endothelium-dependent relaxation in rat aortae from established STZ-induced diabetes.  Br J Pharmacol. 1999;  127 (4) 835-842
    CrossrefPubMedGoogle Scholar
  • 13 Kobayashi T, Kaneda A, Kamata K. Possible involvement of IGF-1 receptor and IGF-binding protein in insulin-induced enhancement of noradrenaline response in diabetic rat aorta.  Br J Pharmacol. 2003;  140 (2) 285-294
    CrossrefPubMedGoogle Scholar
  • 14 Testa R, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A. Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype.  Br J Pharmacol. 1995;  114 (4) 745-750
    PubMedGoogle Scholar
  • 15 Peredo H A, Feleder E C, Adler-Graschinsky E. Time-course of the alterations in prostanoid production and in contractile responses of mesenteric beds isolated from streptozotocin diabetic rats.  Prostaglandins Leukot Essent Fatty Acids. 1999;  60 (4) 269-274
    CrossrefPubMedGoogle Scholar
  • 16 Furman B L, Sneddon P. Endothelium-dependent vasodilator responses of the isolated mesenteric bed are preserved in long-term streptozotocin diabetic rats.  Eur J Pharmacol. 1993;  232 (1) 29-34
    CrossrefPubMedGoogle Scholar
  • 17 Makino A, Kamata K. Possible modulation by endothelin-1, nitric oxide, prostaglandin I2 and thromboxane A2 of vasoconstriction induced by an alpha-agonist in mesenteric arterial bed from diabetic rats.  Diabetologia. 1998;  41 (12) 1410-1418
    CrossrefPubMedGoogle Scholar
  • 18 Taylor P D, Oon B B, Thomas C R, Poston L. Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline-induced contractility in mesenteric resistance arteries from streptozotocin-induced diabetic rats.  Br J Pharmacol. 1994;  111 (1) 35-41
    PubMedGoogle Scholar
  • 19 Taylor P D, Graves J E, Poston L. Selective impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated resistance arteries of the streptozotocin-induced diabetic rat.  Clin Sci (Lond). 1995;  88 (5) 519-524
    PubMedGoogle Scholar
  • 20 Scarborough N L, Carrier G O. Increased alpha 2-adrenoreceptor mediated vascular contraction in diabetic rats.  J Auton Pharmacol. 1983;  3 (3) 177-183
    PubMedGoogle Scholar
  • 21 Griffith T M. Endothelium-dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis?.  Br J Pharmacol. 2004;  141 (6) 881-903
    CrossrefPubMedGoogle Scholar
  • 22 Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte P M, Weston A H. EDHF: bringing the concepts together.  Trends Pharmacol Sci. 2002;  23 (8) 374-380
    CrossrefPubMedGoogle Scholar
  • 23 Diederich D, Skopec J, Diederich A, Dai F X. Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals.  Am J Physiol. 1994;  266 (3 Pt 2) H1153-H1161
    PubMedGoogle Scholar
  • 24 Pieper G M, Langenstroer P, Siebeneich W. Diabetic-induced endothelial dysfunction in rat aorta: role of hydroxyl radicals.  Cardiovasc Res. 1997;  34 (1) 145-156
    CrossrefPubMedGoogle Scholar
  • 25 Wigg S J, Tare M, Tonta M A, O"Brien R C, Meredith I T, Parkington H C. Comparison of effects of diabetes mellitus on an EDHF-dependent and an EDHF-independent artery.  Am J Physiol Heart Circ Physiol. 2001;  281 (1) H232-H240
    PubMedGoogle Scholar
  • 26 Fukao M, Hattori Y, Kanno M, Sakuma I, Kitabatake A. Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats.  Br J Pharmacol. 1997;  121 (7) 1383-1391
    CrossrefPubMedGoogle Scholar
  • 27 Matsumoto T, Kobayashi T, Kamata K. Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats.  Am J Physiol Heart Circ Physiol. 2003;  285 (1) H283-H291
    PubMedGoogle Scholar
  • 28 Matsumoto T, Wakabayashi K, Kobayashi T, Kamata K. Diabetes-related changes in cAMP-dependent protein kinase activity and decrease in relaxation response in rat mesenteric artery.  Am J Physiol Heart Circ Physiol. 2004;  287 (3) 1064-1071
    CrossrefPubMedGoogle Scholar
  • 29 Goto Y, Kakizaki M, Masaki N. Production of spontaneous diabetic rats by repetition of selective breeding.  Tohoku J Exp Med. 1976;  119 (1) 85-90
    PubMedGoogle Scholar
  • 30 Kobayashi T, Matsumoto T, Ooishi K, Kamata K. Differential expression of alpha2D-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats.  Am J Physiol Heart Circ Physiol. 2004;  287 (1) H135-H143
    CrossrefPubMedGoogle Scholar
  • 31 Witte K, Jacke K, Stahrenberg R, Arlt G, Reitenbach I, Schilling L, Lemmer B. Dysfunction of soluble guanylyl cyclase in aorta and kidney of Goto-Kakizaki rats: influence of age and diabetic state.  Nitric Oxide. 2002;  6 (1) 85-95
    CrossrefPubMedGoogle Scholar
  • 32 Witte K, Reitenbach I, Stolpe K, Schilling L, Kirchengast M, Lemmer B. Effects of the endothelin a receptor antagonist darusentan on blood pressure and vascular contractility in type 2 diabetic Goto-Kakizaki rats.  J Cardiovasc Pharmacol. 2003;  41 (6) 890-896
    CrossrefPubMedGoogle Scholar
  • 33 Cheng Z J, Vaskonen T, Tikkanen I, Nurminen K, Ruskoaho H, Vapaatalo H, Muller D, Park J K, Luft F C, Mervaala E M. Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats.  Hypertension. 2001;  37 (2 Part 2) 433-439
    PubMedGoogle Scholar
  • 34 Esmon C T. Why do animal models (sometimes) fail to mimic human sepsis?.  Crit Care Med. 2004;  32 (5 Suppl) S219-S222
    PubMedGoogle Scholar
  • 35 Cipolla M J, Harker C T, Porter J M. Endothelial function and adrenergic reactivity in human type-II diabetic resistance arteries.  J Vasc Surg. 1996;  23 (5) 940-949
    PubMedGoogle Scholar
  • 36 Caballero A E, Arora S, Saouaf R, Lim S C, Smakowski P, Park J Y, King G L, LoGerfo F W, Horton E S, Veves A. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.  Diabetes. 1999;  48 (9) 1856-1862
    CrossrefPubMedGoogle Scholar

Prof. C. Aalkjær

The Water and Salt Research Center, Institute of Physiology and Biophysics ·

University of Aarhus · 8000 Aarhus C · Denmark

Phone: +45 8942 2804

Email: ca@fi.au.dk

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