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Published in: Journal of Anesthesia 4/2018

01-08-2018 | Original Article

Endothelium-dependent vasodilation in the cerebral arterioles of rats deteriorates during acute hyperglycemia and then is restored by reducing the glucose level

Authors: Kazuhiro Kito, Kumiko Tanabe, Koji Sakata, Naokazu Fukuoka, Kiyoshi Nagase, Mami Iida, Hiroki Iida

Published in: Journal of Anesthesia | Issue 4/2018

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Abstract

Purpose

Acute hyperglycemia in patients with traumatic brain injury correlates with a poor neurological outcome. We investigated the endothelium function of rat cerebral arterioles during acute hyperglycemia and after reducing the glucose levels using insulin. We also examined whether or not oxidative stress was involved in the cerebral arteriole response to acute hyperglycemia.

Methods

In isoflurane-anesthetized, mechanically ventilated rats, we used closed cranial window preparation to measure the changes in the pial arteriolar diameter following the topical application of acetylcholine (ACh) or adenosine. We examined the pial arteriolar vasodilator response before hyperglycemia, during hyperglycemia, and after reducing the glucose level using insulin. After intravenous pretreatment with an NADPH oxidase inhibitor (apocynin or diphenylene iodonium), we reexamined the pial arteriolar vasodilator response following the topical application of ACh.

Results

Under control conditions, the topical application of ACh dose-dependently dilated the cerebral arterioles. The vasodilatory responses to topical ACh were impaired during hyperglycemia and improved after the administration of insulin. The vasodilatory responses to topical adenosine were not affected by the glucose levels. In the apocynin or diphenylene iodonium pretreatment group, the topical application of ACh dilated the cerebral arterioles during hyperglycemia.

Conclusion

Acute hyperglycemia induces a dysfunction of the endothelium-dependent vasodilation of rat cerebral arterioles. The dysfunction can be reversed by improving the acute hyperglycemia and it can be prevented entirely by the administration of NADPH oxidase inhibitors. These results could suggest that controlling the glucose levels works protectivity to endothelium function of cerebral arterioles.
Literature
1.
go back to reference Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332(7533):73–8.CrossRefPubMedPubMedCentral Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332(7533):73–8.CrossRefPubMedPubMedCentral
2.
go back to reference Bottle A, Millett C, Khunti K, Majeed A. Trends in cardiovascular admissions and procedures for people with and without diabetes in England, 1996–2005. Diabetologia. 2009;52(1):74–80.CrossRefPubMed Bottle A, Millett C, Khunti K, Majeed A. Trends in cardiovascular admissions and procedures for people with and without diabetes in England, 1996–2005. Diabetologia. 2009;52(1):74–80.CrossRefPubMed
3.
go back to reference Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28(2):103–17.CrossRefPubMed Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28(2):103–17.CrossRefPubMed
4.
go back to reference DECODE Study Group tEDEG. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161(3):397–405.CrossRef DECODE Study Group tEDEG. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161(3):397–405.CrossRef
5.
go back to reference Jones KW, Cain AS, Mitchell JH, Millar RC, Rimmasch HL, French TK, Abbate SL, Roberts CA, Stevenson SR, Marshall D, Lappé DL. Hyperglycemia predicts mortality after CABG: postoperative hyperglycemia predicts dramatic increases in mortality after coronary artery bypass graft surgery. J Diabetes Complicat. 2008;22(6):365–70.CrossRefPubMed Jones KW, Cain AS, Mitchell JH, Millar RC, Rimmasch HL, French TK, Abbate SL, Roberts CA, Stevenson SR, Marshall D, Lappé DL. Hyperglycemia predicts mortality after CABG: postoperative hyperglycemia predicts dramatic increases in mortality after coronary artery bypass graft surgery. J Diabetes Complicat. 2008;22(6):365–70.CrossRefPubMed
6.
go back to reference Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G. Nishigaki. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057–69.CrossRefPubMedPubMedCentral Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G. Nishigaki. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057–69.CrossRefPubMedPubMedCentral
7.
go back to reference Mah E, Noh SK, Ballard KD, Matos ME, Volek JS, Bruno RS. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine. J Nutr. 2011;141(11):1961–8.CrossRefPubMed Mah E, Noh SK, Ballard KD, Matos ME, Volek JS, Bruno RS. Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine. J Nutr. 2011;141(11):1961–8.CrossRefPubMed
8.
go back to reference Affonso FS, Cailleaux S, Pinto LF, Gomes MB, Tibiriçá E. Effects of high glucose concentrations on the endothelial function of the renal microcirculation of rabbits. Arq Bras Cardiol. 2003;81(2):161–5.CrossRef Affonso FS, Cailleaux S, Pinto LF, Gomes MB, Tibiriçá E. Effects of high glucose concentrations on the endothelial function of the renal microcirculation of rabbits. Arq Bras Cardiol. 2003;81(2):161–5.CrossRef
9.
go back to reference Sogawa K, Nagaoka T, Izumi N, Nakabayashi S, Yoshida A. Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats. Invest Ophthalmol Vis Sci. 2010;51(5):2648–55.CrossRefPubMed Sogawa K, Nagaoka T, Izumi N, Nakabayashi S, Yoshida A. Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats. Invest Ophthalmol Vis Sci. 2010;51(5):2648–55.CrossRefPubMed
10.
go back to reference Azuma K, Kawamori R, Toyofuku Y, Kitahara Y, Sato F, Shimizu T, Miura K, Mine T, Tanaka Y, Mitsumata M, Watada H. Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol. 2006;26(10):2275–80.CrossRefPubMed Azuma K, Kawamori R, Toyofuku Y, Kitahara Y, Sato F, Shimizu T, Miura K, Mine T, Tanaka Y, Mitsumata M, Watada H. Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol. 2006;26(10):2275–80.CrossRefPubMed
11.
go back to reference Didion SP, Lynch CM, Baumbach GL, Faraci FM. Impaired endothelium-dependent responses and enhanced influence of Rho-kinase in cerebral arterioles in type II diabetes. Stroke. 2005;36(2):342–7.CrossRefPubMed Didion SP, Lynch CM, Baumbach GL, Faraci FM. Impaired endothelium-dependent responses and enhanced influence of Rho-kinase in cerebral arterioles in type II diabetes. Stroke. 2005;36(2):342–7.CrossRefPubMed
12.
go back to reference Tan S, Zhi PK, Luo ZK, Shi J. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia. Neuroscience. 2015;303:138–48.CrossRefPubMed Tan S, Zhi PK, Luo ZK, Shi J. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia. Neuroscience. 2015;303:138–48.CrossRefPubMed
13.
go back to reference Cipolla MJ, Godfrey JA. Effect of hyperglycemia on brain penetrating arterioles and cerebral blood flow before and after ischemia/reperfusion. Transl Stroke Res. 2010;1(2):127–34.CrossRefPubMedPubMedCentral Cipolla MJ, Godfrey JA. Effect of hyperglycemia on brain penetrating arterioles and cerebral blood flow before and after ischemia/reperfusion. Transl Stroke Res. 2010;1(2):127–34.CrossRefPubMedPubMedCentral
14.
go back to reference Nakahata K, Kinoshita H, Azma T, Matsuda N, Hama-Tomioka K, Haba M, Hatano Y. Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress. Anesthesiology. 2008;108(2):269–75.CrossRefPubMed Nakahata K, Kinoshita H, Azma T, Matsuda N, Hama-Tomioka K, Haba M, Hatano Y. Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress. Anesthesiology. 2008;108(2):269–75.CrossRefPubMed
15.
go back to reference Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295(14):1681–7.CrossRefPubMed Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295(14):1681–7.CrossRefPubMed
16.
go back to reference Mah E, Bruno RS. Postprandial hyperglycemia on vascular endothelial function: mechanisms and consequences. Nutr Res. 2012;32(10):727–40.CrossRefPubMed Mah E, Bruno RS. Postprandial hyperglycemia on vascular endothelial function: mechanisms and consequences. Nutr Res. 2012;32(10):727–40.CrossRefPubMed
17.
go back to reference Hayashi T, Juliet PA, Kano-Hayashi H, Tsunekawa T, Dingqunfang D, Sumi D, Matsui-Hirai H, Fukatsu A, Iguchi A. NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent and -independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction. Diabetes Obes Metab. 2005;7(4):334–43.CrossRefPubMed Hayashi T, Juliet PA, Kano-Hayashi H, Tsunekawa T, Dingqunfang D, Sumi D, Matsui-Hirai H, Fukatsu A, Iguchi A. NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent and -independent responses and scavenges superoxide anion in rats with type 2 diabetes complicated by NO dysfunction. Diabetes Obes Metab. 2005;7(4):334–43.CrossRefPubMed
18.
go back to reference Iida H, Iida M, Takenaka M, Fukuoka N, Dohi S. Comparative effects of cilostazol and aspirin on the impairment of endothelium-dependent cerebral vasodilation caused by acute cigarette smoking in rats. J Thromb Thrombolysis. 2010;29(4):483–8.CrossRefPubMed Iida H, Iida M, Takenaka M, Fukuoka N, Dohi S. Comparative effects of cilostazol and aspirin on the impairment of endothelium-dependent cerebral vasodilation caused by acute cigarette smoking in rats. J Thromb Thrombolysis. 2010;29(4):483–8.CrossRefPubMed
19.
go back to reference Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6.CrossRefPubMed Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6.CrossRefPubMed
20.
go back to reference Ongini E, Fredholm BB. Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci. 1996;17(10):364 – 72.CrossRefPubMed Ongini E, Fredholm BB. Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci. 1996;17(10):364 – 72.CrossRefPubMed
21.
go back to reference Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Circulation. 2003;108(12):1527–32.CrossRefPubMed Creager MA, Lüscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Circulation. 2003;108(12):1527–32.CrossRefPubMed
22.
go back to reference Sercombe R, Vicaut E, Oudart N, Sercombe C, Girard P. Acetylcholine-induced relaxation of rabbit basilar artery in vitro is rapidly reduced by reactive oxygen species in acute hyperglycemia: role of NADPH oxidase. J Cardiovasc Pharmacol. 2004;44(4):507–16.CrossRefPubMed Sercombe R, Vicaut E, Oudart N, Sercombe C, Girard P. Acetylcholine-induced relaxation of rabbit basilar artery in vitro is rapidly reduced by reactive oxygen species in acute hyperglycemia: role of NADPH oxidase. J Cardiovasc Pharmacol. 2004;44(4):507–16.CrossRefPubMed
23.
go back to reference Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke. 2006;37(1):267–73.CrossRefPubMed Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke. 2006;37(1):267–73.CrossRefPubMed
24.
go back to reference Mao XM, Liu H, Tao XJ, Yin GP, Li Q, Wang SK. Independent anti-inflammatory effect of insulin in newly diagnosed type 2 diabetes. Diabetes Metab Res Rev. 2009;25(5):435–41.CrossRefPubMed Mao XM, Liu H, Tao XJ, Yin GP, Li Q, Wang SK. Independent anti-inflammatory effect of insulin in newly diagnosed type 2 diabetes. Diabetes Metab Res Rev. 2009;25(5):435–41.CrossRefPubMed
25.
go back to reference Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–72.CrossRefPubMed Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–72.CrossRefPubMed
26.
go back to reference Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94(3):1172–9.CrossRefPubMedPubMedCentral Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94(3):1172–9.CrossRefPubMedPubMedCentral
27.
go back to reference Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.CrossRefPubMed Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.CrossRefPubMed
28.
go back to reference Alper G, Olukman M, Irer S, Cağlayan O, Duman E, Yilmaz C, Ulker S. Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat. Diabetes Metab Res Rev. 2006;22(3):190–7.CrossRefPubMed Alper G, Olukman M, Irer S, Cağlayan O, Duman E, Yilmaz C, Ulker S. Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat. Diabetes Metab Res Rev. 2006;22(3):190–7.CrossRefPubMed
30.
go back to reference Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281(5):E924–30.CrossRef Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281(5):E924–30.CrossRef
31.
go back to reference Nyvad J, Mazur A, Postnov DD, Straarup MS, Soendergaard AM, Staehr C, Brøndum E, Aalkjaer C, Matchkov VV. Intravital investigation of rat mesenteric small artery tone and blood flow. J Physiol. 2017;595(15):5037–53.CrossRefPubMedPubMedCentral Nyvad J, Mazur A, Postnov DD, Straarup MS, Soendergaard AM, Staehr C, Brøndum E, Aalkjaer C, Matchkov VV. Intravital investigation of rat mesenteric small artery tone and blood flow. J Physiol. 2017;595(15):5037–53.CrossRefPubMedPubMedCentral
32.
go back to reference Zhong MF, Shen WL, Wang J, Yang J, Yuan WJ, He J, Wu PP, Wang Y, Zhang L, Higashino H, Chen H. Paradoxical effects of streptozotocin-induced diabetes on endothelial dysfunction in stroke-prone spontaneously hypertensive rats. J Physiol. 2011;589(Pt 21):5153–65.CrossRefPubMedPubMedCentral Zhong MF, Shen WL, Wang J, Yang J, Yuan WJ, He J, Wu PP, Wang Y, Zhang L, Higashino H, Chen H. Paradoxical effects of streptozotocin-induced diabetes on endothelial dysfunction in stroke-prone spontaneously hypertensive rats. J Physiol. 2011;589(Pt 21):5153–65.CrossRefPubMedPubMedCentral
Metadata
Title
Endothelium-dependent vasodilation in the cerebral arterioles of rats deteriorates during acute hyperglycemia and then is restored by reducing the glucose level
Authors
Kazuhiro Kito
Kumiko Tanabe
Koji Sakata
Naokazu Fukuoka
Kiyoshi Nagase
Mami Iida
Hiroki Iida
Publication date
01-08-2018
Publisher
Springer Japan
Published in
Journal of Anesthesia / Issue 4/2018
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-018-2507-7

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