Increased haemodynamic adrenergic load with isoflurane anaesthesia in type 2 diabetic and obese rats in vivo

Cardiovascular Diabetology

Regis R Lamberts¹  Anne E de Leeuw¹  Carol T Bussey¹ 

[1] HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand

关键词: in vivo;    Obesity;    Type 2 diabetes;    Haemodynamic;    Conscious;    Anaesthesia;   

Others  :  1118929
DOI  :  10.1186/s12933-014-0161-4

 received in 2014-08-13, accepted in 2014-12-01,  发布年份 2014

【 摘 要 】

Background

Increasing numbers of type 2 diabetic and obese patients with enhanced rates of cardiovascular complications require surgical interventions, however they have a higher incidence of perioperative haemodynamic complications, which has been linked to adrenergic dysfunction. Therefore, we aimed to determine how α- and β-adrenoceptor (AR)-mediated haemodynamic responses are affected by isoflurane anaesthesia in experimental type 2 diabetes and obesity in vivo.

Methods

Sixteen-week old male Zucker type 2 Diabetic Fatty (ZDF) rats, Zucker Obese rats and their lean counterparts (n = 7-9 per group) were instrumented with radio telemeters to record blood pressure and heart rate and with vascular access ports for non-invasive intravenous drug delivery in vivo. Haemodynamic effects of α-AR (phenylephrine; 1-100 μg.kg⁻¹) or β-AR (dobutamine; 2-120 μg.kg⁻¹) stimulation were assessed under conscious and anaesthetised (isoflurane; 2%) conditions.

Results

Vascular α-AR sensitivity was increased in both diabetic (non-diabetic 80 ± 3 vs. diabetic 95 ± 4 ΔmmHg at 100 μg.kg⁻¹; p < 0.05) and obese (lean 65 ± 6 vs. obese 84 ± 6 ΔmmHg at 20 μg.kg⁻¹; p < 0.05) conscious rats. Interestingly, anaesthesia exacerbated and prolonged the increased α-AR function in both diabetic and obese animals (non-diabetic 51 ± 1 vs. diabetic 68 ± 4 ΔmmHg, lean 61 ± 5 vs. obese 84 ± 2 ΔmmHg at 20 μg.kg⁻¹; p < 0.05). Meanwhile, β-AR chronotropic sensitivity was reduced in conscious diabetic and obese rats (non-diabetic 58 ± 7 vs. diabetic 27 ± 8 Δbpm, lean 103 ± 12 vs. obese 61 ± 9 Δbpm at 15 μg.kg⁻¹; p < 0.05). Anaesthesia normalised chronotropic β-AR responses, via either a limited reduction in obese (lean 51 ± 3 vs. obese 66 ± 5 Δbpm; NS at 15 μg.kg⁻¹) or increased responses in diabetic animals (non-diabetic 49 ± 8 vs. diabetic 63 ± 8 Δbpm, at 15 μg.kg⁻¹; NS at 15 μg.kg⁻¹).

Conclusions

Long term metabolic stress, such as during type 2 diabetes and obesity, alters α- and β-AR function, its dynamics and the interaction with isoflurane anaesthesia. During anaesthesia, enhanced α-AR sensitivity and normalised β-AR function may impair cardiovascular function in experimental type 2 diabetes and obesity.

【 授权许可】

   
2014 Bussey et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Alserius T, Hammar N, Nordqvist T, Ivert T: Improved survival after coronary artery bypass grafting has not influenced the mortality disadvantage in patients with diabetes mellitus. J Thorac Cardiovasc Surg 2009, 138(5):1115-1122.
• [2]Tolpin DA, Collard CD, Lee V-V, Elayda MA, Pan W: Obesity is associated with increased morbidity after coronary artery bypass graft surgery in patients with renal insufficiency. J Thorac Cardiovasc Surg 2009, 138(4):873-879.
• [3]Tung A: Anaesthetic considerations with the metabolic syndrome. Br J Anaesth 2010, 105(suppl 1):i24-i33.
• [4]Vinik AI, Ziegler D: Diabetic Cardiovascular Autonomic Neuropathy. Circulation 2007, 115(3):387-397.
• [5]Vohra A, Kumar S, Charlton AJ, Olukoga AO, Boulton AJM, McLeod D: Effect of Diabetes Mellitus on the cardiovascular responses to induction of anaesthesia and tracheal intubation. Br J Anaesth 1993, 71(2):258-261.
• [6]Knüttgen D, Weidemann D, Doehn M: Diabetic autonomic neuropathy: abnormal cardiovascular reactions under general anesthesia. Klin Wochenschr 1990, 68(23):1168-1172.
• [7]Lambert GW, Straznicky NE, Lambert EA, Dixon JB, Schlaich MP: Sympathetic nervous activation in obesity and the metabolic syndrome—Causes, consequences and therapeutic implications. Pharmacol Ther 2010, 126(2):159-172.
• [8]Agapitov AV, Correia MLG, Sinkey CA, Haynes WG: Dissociation Between Sympathetic Nerve Traffic and Sympathetically Mediated Vascular Tone in Normotensive Human Obesity. Hypertension 2008, 52(4):687-695.
• [9]Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF, Mary DASG: Impact of Type 2 Diabetes Mellitus on Sympathetic Neural Mechanisms in Hypertension. Circulation 2003, 108(25):3097-3101.
• [10]Marsh SA, Powell PC, Agarwal A, Dell'Italia LJ, Chatham JC: Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis. Am J Physiol Heart Circ Physiol 2007, 293(1):H292-H298.
• [11]Matsuda N, Hattori Y, Gando S, Akaishi Y, Kemmotsu O, Kanno M: Diabetes-induced down-regulation of β1-adrenoceptor mRNA expression in rat heart. Biochem Pharmacol 1999, 58(5):881-885.
• [12]Bidasee KR, Zheng H, Shao C-H, Parbhu SK, Rozanski GJ, Patel KP: Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors. J Appl Physiol 2008, 105(3):907-914.
• [13]Dinçer ÜD, Bidasee KR, Güner Ş, Tay A, Özçelikay AT, Altan VM: The Effect of Diabetes on Expression of β1-, β2-, and β3-Adrenoreceptors in Rat Hearts. Diabetes 2001, 50(2):455-461.
• [14]Lahaye SLD, Gratas-Delamarche A, Malardé L, Vincent S, Zguira MS, Morel SL, Delamarche P, Zouhal H, Carré F, Bekono FR: Intense exercise training induces adaptation in expression and responsiveness of cardiac β-adrenoceptors in diabetic rats. Cardiovasc Diabetol 2010, 9:72. BioMed Central Full Text
• [15]Dinçer ÜD, Onay A, Arı N, Özçelikay AT, Altan VM: The effects of diabetes on β-adrenoceptor mediated responsiveness of human and rat atria. Diabetes Res Clin Pract 1998, 40(2):113-122.
• [16]Amour J, David J-S, Vivien B, Coriat P, Riou B: Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium. Anesthesiology 2004, 101(5):1145-1152.
• [17]Lamberts RR, Lingam SJ, Wang H-Y, Bollen IA, Hughes G, Galvin IF, Bunton RW, Bahn A, Katare R, Baldi JC, Williams MJ, Saxena P, Coffey S, Jones PP: Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovasc Diabetol 2014, 13:72. BioMed Central Full Text
• [18]Buñag RD, Tomita T, Krizsan D: Renovascular beta adrenergic hypersensitivity and hyperinsulinemia in rats with dietary-induced obesity. J Pharmacol Exp Ther 1990, 255(1):325-332.
• [19]Strassheim D, Houslay MD, Milligan G: Regulation of cardiac adenylate cyclase activity in rodent models of obesity. Biochem J 1992, 283(1):203-208.
• [20]Chatelain P, Robberecht P, Neef P, Camus J-C, Poloczek P, Christophe J: Impairment of Hormone-Stimulated cardiac adenylate cyclase activity in the genetically obese (fa/fa) Zucker rat. Pflügers Archives 1981, 390(1):10-16.
• [21]Ruggeri P, Brunori A, Cogo CE, Storace D, Di Nardo F, Burattini R: Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat. Am J Physiol Regul Integr Comp Physiol 2006, 291(2):R376-R382.
• [22]Mita M, Kuramoto T, Ito K, Toguchi-Senrui N, Hishinuma S, Walsh MP, Shoji M: Impairment of α1-adrenoceptor-mediated contractile activity in caudal arterial smooth muscle from Type 2 diabetic Goto-Kakizaki rats. Clin Exp Pharmacol Physiol 2010, 37(3):350-357.
• [23]Schreihofer AM, Hair CD, Stepp DW: Reduced plasma volume and mesenteric vascular reactivity in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 2004, 288(1):R253-R261.
• [24]Naik J, Xiang L, Hester R: Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 2006, 290(1):R154-R161.
• [25]Naik J, Xiang L, Hodnett B, Hester R: Alpha-adrenoceptor-mediated vasoconstriction is not involved in impaired functional vasodilation in the obese Zucker rat. Clin Exp Pharmacol Physiol 2008, 35(5–6):611-616.
• [26]Després J-P: Targeting abdominal obesity and the metabolic syndrome to manage cardiovascular disease risk. Heart 2009, 95(13):1118-1124.
• [27]Oakley I, Emond L: Diabetic cardiac autonomic neuropathy and anesthetic management: review of the literature. AANA J 2011, 79(6):473-479.
• [28]Kasai T, Hirose M, Matsukawa T, Takamata A, Tanaka Y: The vasoconstriction threshold is increased in obese patients during general anaesthesia. Acta Anaesthesiol Scand 2003, 47(5):588-592.
• [29]Crespo MJ, Marrero M, Cruz N, Quidgley J, Creagh O, Torres H, Rivera K: Diabetes alters cardiovascular responses to anaesthetic induction agents in STZ-diabetic rats. Diab Vasc Dis Res 2011, 8(4):299-302.
• [30]van den Brom CE, Bulte CS, Loer SA, Bouwman RA, Boer C: Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism. Cardiovasc Diabetol 2013, 12:42. BioMed Central Full Text
• [31]Bulte C, van den Brom C, Loer S, Boer C, Bouwman R: Myocardial blood flow under general anaesthesia with sevoflurane in type 2 diabetic patients: a pilot study. Cardiovasc Diabetol 2014, 13:62. BioMed Central Full Text
• [32]Yoshimoto T, Eguchi K, Sakurai H, Ohmichi Y, Hashimoto T, Ohmichi M, Morimoto A, Yamaguchi Y, Ushida T, Iwase S, Sugenoya J, Kumazawa T: Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats. J Physiol Sci 2011, 61(5):373-383.
• [33]Huber DA, Schreihofer AM: Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms. J Physiol 2010, 588(9):1515-1525.
• [34]Bussey CT, de Leeuw AE, Cook RF, Ashley Z, Schofield J, Lamberts RR: Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats. Lab Anim 2014, 48(3):250-260.
• [35]Paulsen SJ, Vrang N, Larsen LK, Larsen PJ, Jelsing J: Stereological assessment of pancreatic beta-cell mass development in male Zucker Diabetic Fatty (ZDF) rats: correlation with pancreatic beta-cell function. J Anat 2010, 217(5):624-630.
• [36]Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CT, Hess JF: Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet 1996, 13:18-19.
• [37]Chua SC, White DW, Wu-Peng XS, Liu S-M, Okada N, Kershaw EE, Chung WK, Power-Kehoe L, Chua M, Tartaglia LA, Leibel RL: Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 1996, 45(8):1141-1143.
• [38]Lucchinetti E, Aguirre J, Feng J, Zhu M, Suter M, Spahn DR, Härter L, Zaugg M: Molecular Evidence of Late Preconditioning After Sevoflurane Inhalation in Healthy Volunteers. Anesth Analg 2007, 105(3):629-640.
• [39]Radovits T, Korkmaz S, Loganathan S, Barnucz E, Bömicke T, Arif R, Karck M, Szabó G: Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 2009, 297(1):H125-H133.
• [40]Overgaard CB, Džavík V: Inotropes and Vasopressors: Review of Physiology and Clinical Use in Cardiovascular Disease. Circulation 2008, 118(10):1047-1056.
• [41]Pousset F, Chalon S, Thomaré P, Diquet B, Lechat P: Evaluation of cardiac beta 1-adrenergic sensitivity with dobutamine in healthy volunteers. Br J Clin Pharmacol 1995, 39(6):633-639.
• [42]Carroll J, Kyser C, Martin M: beta-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts. Int J Obes Relat Metab Disord 2002, 26(5):627-632.
• [43]Leung JYT, Kwok EWY, Liu GY, Pang CCY: Attenuated α-adrenoceptor-mediated arterial and venous constrictions in rat models of diabetes. Eur J Pharmacol 2010, 642(1–3):128-133.
• [44]Song D, Hutchings SR, Pang CCY: Impaired in vivo venous constriction in conscious obese Zucker rats with metabolic syndrome. Naunyn-Schmied Arch Pharmacol 2006, 373(6):451-456.
• [45]Falcão-Pires I, Fontes-Sousa A, Lopes-Conceiçao L, Brás-Silva C, Leite-Moreira A: Modulation of myocardial stiffness by β-adrenergic stimulation–its role in normal and failing heart. Physiol Res 2011, 60(4):599-609.
• [46]Kamata K, Satoh T, Matsumoto T, Noguchi E, Taguchi K, Kobayashi T, Tanaka H, Shigenobu K: Enhancement of methoxamine-induced contractile responses of rat ventricular muscle in streptozotocin-induced diabetes is associated with α1A adrenoceptor upregulation. Acta Physiol 2006, 188(3–4):173-183.
• [47]Novielli NM, Al-Khazraji BK, Medeiros PJ, Goldman D, Jackson DN: Pre-Diabetes Augments Neuropeptide Y1- and α1- Receptor Control of Basal Hindlimb Vascular Tone in Young ZDF Rats. PLoS ONE 2012, 7(10):e46659.
• [48]Edith-Rodriguez J, Resendiz-Albor AA, Arciniega-Martinez IM, Campos-Rodriguez R, Hong E, Huang F, Villafaña S: Effect of Early Diabetes on the Expression of Alpha-1 Adrenergic Receptors in Aorta and Carotid Arteries of Wistar Kyoto and Spontaneously Hypertensive Rats. Clin Exp Hypertens 2013, 35(6):389-395.
• [49]Schulingkamp RJ, Aloyo V, Tallarida RJ, Raffa RB: Changes in Aorta Alpha1-Adrenoceptor Number and Affinity during One Year of Streptozotocin-Induced Diabetes in Rats. Pharmacology 2005, 74:23-30.
• [50]Gando S, Hattori Y, Akaishi Y, Nishihira J, Kanno M: Impaired Contractile Response to Beta Adrenoceptor Stimulation in Diabetic Rat Hearts: Alterations in BetaAdrenoceptors-G Protein-Adenylate Cyclase System and Phospholamban Phosphorylation. J Pharmacol Exp Ther 1997, 282(1):475-484.
• [51]Lesniewski LA, Donato AJ, Behnke BJ, Woodman CR, Laughlin MH, Ray CA, Delp MD: Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension. Am J Physiol Heart Circ Physiol 2008, 294(4):H1840-H1850.
• [52]Avelar E, Cloward TV, Walker JM, Farney RJ, Strong M, Pendleton RC, Segerson N, Adams TD, Gress RE, Hunt SC, Litwin SE: Left Ventricular Hypertrophy in Severe Obesity: Interactions Among Blood Pressure, Nocturnal Hypoxemia, and Body Mass. Hypertension 2007, 49(1):34-39.