Relaxation Responses of Ketamine and Propofol to Vasoactive Agents in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetes mellitus (DM) is a major risk factor for the development of endothelial dysfunction which affects the ability of blood vessels to regulate vascular tone. The study aimed to investigate the mechanisms of vasodilator action of the anaesthetic agents ketamine and propofol in diabetic rat aorta. 30 male Sprague-Dawley rats were randomly divided into two equal groups: (i) non-diabetic control (ii) Streptozotocin-induced diabetic group. DM was induced by a single intra-peritoneal injection of streptozotocin at 50 mg/kg body weight.  Blood samples were taken from the tail vein after 24 hours and tested for glucose level using an automated glucose analyser. A blood glucose ≥10 mmol/L confirmed hyperglycaemia and the development of DM.  Rats were  sacrificed, and the aortae excised.  The vascular responses of  aortic rings from both groups to ketamine, propofol in the presence of  vasoactive agents  were studied using standard organ bath procedures. Ketamine and propofol reduced Phe-induced contraction similarly in the diabetic and control groups. Barium chloride, attenuated the relaxation response to propofol in diabetic aorta when compared to ketamine. 4-aminopyridine significantly attenuated the relaxation response to ketamine and propofol in diabetic aorta. Glibenclamide, significantly reduced  ketamine-induced relaxation in diabetic aorta when compared to propofol. Activation of K+ channels with nicorandil or NS1619 did not affect the relaxation response to ketamine or propofol in diabetic aorta. The results recommend that propofol can be effective in mitigating the consequences of hemodynamic instability in glibenclamide treated diabetics when compared to ketamine. This response is mediated by propofol-induced inhibition of intracellular calcium influx.

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References

Chai, Q., Liu, Z., & Chen, L. (2005). Effects of streptozotocin-induced diabetes on Kv channels in rat small coronary smooth muscle cells. Chinese J of Physiol., 48(1):57-63.

Chan, W.K., Yao, X., Ko, W. H. & Huang, Y. (2000). Nitric oxide mediated endlthelium-dependent relaxation induced by glibenclamide in rat isolated aorta. Oxford Journals of cardiovasc Res, 46(1): 180-187.

Chittari, M. V., McTeman, P., Bawazeer, N., Constantinides, K., Ciotola, M., O’Hare, J. P.,... Ceriello, A. (2010). The impact of acute hyperglycaemia on endothelial function and retinal vascular reactivity in patients with type 2 diabetes. Diabet med., 1464-5491.03223.

Cifuentes F, Palacios J, Paredes A, Nwokocha CR, Paz C. 8-Oxo-9-Dihydromakomakine Isolated from Aristotelia chilensis Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx. Molecules. 2018;23(11):3050.

Dhanavathy, G. (2015). Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoirdiod glycoside, prevents and protects streptozotocin-induced ß-cell damage in Wister rat pancreas. J Endocrinol Invest. 38(6):669-84.

Ding, H., & Tringle, C. (2005). Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium. Vasc Health Risk Manag. 1(1):55-71.

Ertuna, E., & Yasa, M. (2005). Vasorelaxant effects of glibenclamide on rat thoracic aorta. J. Fac. Pharm, Ankara. 34(2):119-128.

Gribble, F. M., & Reimann, F. (2003). Sulphonylurea action revisited: The post-cloning era. Diabetologia, 46(7):875-91

Hao, N., Deng, C. Y., Kuang, S. J., Ma, J., Zhang, G. Y., Cui, J. X. (2017). Effects of propofol combined with indomethacin on contraction of isolated human pulmonary arteries. Nan Fang Yi Ke Da Xue Xue Bao. 20:37(3):342-346.

Ibeawuchi, C. U., Ajayi, O. I., & Ebeigbe, A. B. (2008). Vascular effect of ketamine in isolated rabbit aortic smooth muscle. Niger J Physiol Sci., 23(1-2):85-88.

Jackson, W. F. (2000). Ion channels and vascular tone. Hypertension, 35(1Pt.2):173-178.

Kawano, T., Oshita, S., Takahashi, A., Tsutsumi, Y., Tanaka, K., ..., & Nakaya, Y. (2005). Molecular mechanisms underlying ketamine-mediated inhibition of sarcolemmal adenosine triphosphate-sensitive potassium channels. Anaesthesiology. 102: 93-101.

Kawano, T., Tanaka, K., Yinhua, Eguchi, S., Kawano, H., & Oshita, S. (2010). Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell derived from rat aortic smooth muscle. J of Medical Investi., 57(3-4): 237-44.

Kim, S. H., Bae, Y. M., Sung, D. J., Park, S. W., Woo, N. S., Kim, B., & Cho, S. I. (2007). Ketamine blocks voltage-gated K (+) channels and causes membrane depolarization in rat mesenteric artery myocytes. Pflugers Arch., 45(6):891-902.

Liwa, A. C., Barton, E. N., Cole, W. C., & Nwokocha, C. R. (2017). Bioactive plant molecules, sources and mechanism of action in the treatment of cardiovascular disease. In Pharmacognosy (pp. 315-336). Academic Press.

Nwokocha, C. R., Ajayi, I. O., & Ebeigbe, A. B. (2011). Altered vascular reactivity induced by malaria parasites. West Indian Med.J. 60(1):13-8.

Nwokocha, C. R., Owu, D. U., Ajayi, I. O., Ebeigbe, A. B., & Nwokocha, M. I. (2012). Experimental malaria: the in vitro and in vivo blood pressure paradox. Cardiovascular journal of Africa, 23(2), 98.

Owu DU, Orie NN, Nwokocha CR, Muzyamba M, Clapp LH, Osim EE. Attenuated vascular responsiveness to K+ channel openers in diabetes mellitus: the differential role of reactive oxygen species. Gen Physiol Biophys. 2013;32(4):527-534.

Park, S., Kang, H. J., Jeron, J. H., Kim, M. J., Lee, l. K. (2019). Recent advances in the pathogenesis of microvascular complications in diabetes. Arch Pharm Res. 42(3):252-262

Potenza, M. A., Gagliardi, S., Nacci, C., carratu, M. R. & Montagnan, M. (2009). Endothelial dysfunction in diabetes: from mechanisms to therapeutic tatgets. Curr Med Chem, 16(1):94-112.

Reid, M., Spence, J., Nwokocha, M., Palacios, J., & Nwokocha, C. R. (2018). The Role of NADP (H) Oxidase Inhibition and Its Implications in Cardiovascular Disease Management Using Natural Plant Products. In Studies in Natural Products Chemistry (Vol. 58, pp. 43-59). Elsevier.

Romero F, Palacios J, Jofré I, et al. Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta. Molecules. 2019;24(15):2748.

Schulingkamp, R. J., Aloyo, V., Tallarida, R. J., & Raffa, R. B. (2005). Changes in aorta alpha 1-adrenoceptor number and affinity during one year of streptozotocin-induced diabetes in rats. Pharmacology. 74:23-30.

Sobey, C. G. (2001). Potassium channel function in vascular disease. Arterioscler Throm Vasc Biol., 21(1):28-38.

Tsao, C. M., Chen, S. J., Tsou, M. Y., & Wu, C. C. (2012). Effect of propofol on vascular reactivity in thoracic aortas fromm rats with endotoxemia. J Chin Med Assoc. 75(6):262-8.

Zhu, B. H., Guan, Y. Y., Min, J., & He, H. (2001). Contractile responses of diabetic rat aorta to phenylephrine at different stages of diabetic duration. Acta Pharmacol Sin. (5):445-9.

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