흰쥐에서 혈관내피 의존적인 혈관이완과 혈압하강에 대한 propofol의 억제 효과

Inhibitory effect of propofol on endothelium-dependent relaxation and blood pressure lowering in rats

  • 김상진 (전북대학교 생체안전성연구소) ;
  • 김정곤 (전북대학교 생체안전성연구소) ;
  • 조성건 (전북대학교 생체안전성연구소) ;
  • 강형섭 (전북대학교 생체안전성연구소) ;
  • 김진상 (전북대학교 생체안전성연구소)
  • Kim, Shang-Jin (Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Jeong-gon (Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University) ;
  • Joe, Sung-gun (Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University) ;
  • Kang, Hyung-sub (Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Jin-shang (Department of Pharmacology, College of Veterinary Medicine, Chonbuk National University)
  • 심사 : 2004.05.28
  • 발행 : 2004.09.30

초록

We studied the effect of propofol (PPF) on the endothelium-dependent vascular responses in isolated rat thoracic aorta. In aortic rings with endothelium, PPF inhibited the phenylephrine (PE)-induced contraction in a concentration-dependent manner. In PE-precontracted preparations, PPF attenuated the endothelium-dependent relaxation by acetylcholine but not by A23187. And PPF did not attenuate the endothelium-independent relaxation by sodium nitroprusside (SNP). The relaxation induced by acetylcholine in PE-precontracted aortic rings was significantly augmented by zaprinast, a cGMP-specific phosphodiesterase inhibitor, and this augmentation was inhibited by PPF. Although SNP-induced relaxation was significantly augmented by zaprinast, this augmentation was not inhibited by PPF. In preparations preconstricted with PE, the PPF-induced relaxation was inhibited by atropine. In addition, PPF attenuated the vasorelaxation by phosphodiesterase inhibitors (IBMX, Ro20-1724 or zaprinast except milrinone). In vivo, the infusion of acetylcholine and SNP showed decreased arterial blood pressure in rats. The pre-injection of PPF inhibited the acetylcholine-induced blood pressure lowering, but not the SNP-induced blood pressure lowering. These results suggest that PPF can attenuate in part the acetylcholine-induced vasorelaxation and blood pressure lowering through the inhibition of the acetylcholine receptor-mediated endothelium-derived relaxing factor by acting on endothelium. It is considered that the inhibitory effect of PPF on the vasorelaxation is due to the decreased level of cGMP which can be attributed to the inhibition of the muscarinic receptor and/or receptor-G-protein interaction.

키워드

참고문헌

  1. Boillot, A., Laurant, P., Berthelot, A. and Barale, F. Effect of propofol in vascular reactivity in isolated aortae from normotensive and spontaneously hypertensiverats. Br. J. Anaesth. 1999, 83, 622-629
  2. Claeys, M. A., Gepts, E. and Camu, F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br. J. Anaesth. 1988, 60, 3-9
  3. Flavahan, N. A. and Vanhoutte, P. M. Endothelial cell signaling and endothelial dysfunction. Am. J. Hypertens. 1995, 8, 285-418
  4. Furchgott, R. F. and Vanhoutte, P. M. Endotheliumderived relaxing and contraction factors. FASEB J. 1989, 3, 2007-2018
  5. Furuya, R., Oka, K., Watanabe, I., Kamiya, Y., Itoh, H. and Andoh, T. The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptorsand $P_{2x}$ purinoceptors in PCI2 cells. Anesth. Analg. 1999, 88, 174-180
  6. Gelb, A. W., Zhang, C. and Hamilton, J. T. Propofol induces dilation and inhibits constriction in guinea pig basilar arteries. Anesth. Analg. 1996, 83, 472-476
  7. Grounds, R. M., Twigley, A. J., Carli, F., Whithwam, J. G. and Morgan, M. The haemodynamic effects of intravenous induction. Anaesthesia. 1985, 40, 735-740
  8. Harrison, S. A., Chang, M. L. and Beavo, J. A. Differential inhibition of cardiac cyclic nucleotide phosphodiesterase isozymes by cardiotonic drugs. Circulation. 1986, 73(3 Pt 2)III, 109-116
  9. Horibe, M., Ogawa, K., Shon, J. T. and Murray, P. A. Propofol attenuates acetylcholine-induced pulmonary vasorelaxation: Role of nitric oxide and endotheliumderived Hyperpolarizing. Anesthesiology. 2000, 93, 447-455
  10. Hutcheson, I. R. and Griffith, T. M. Central role of intracellular calcium stores in acute flow- and agonistevoked endothelial nitric oxide release. Br. J. Pharmacol.1997, 122, 117-125
  11. Ilkiw, J. E., Pascoe, P. J., Haskin, S. C. and Patz, J. D. Cardiovascular and respiratory effects of propofol administration in hypovolemic dogs. Am. J. Vet. Res. 1992, 12, 2323-2327
  12. Imura, N., Shiraishi, Y., Katsuya, H. and Itoh, T. Effect of propofol on norepinephrine-induced increases in $[Ca^{2+}]_{i}$ and force in smooth muscle of the rabbit mesenteric resistance artery. Anesthesiology. 1998, 88, 1566-1578
  13. Iranami, H., Hatano, Y., Tsukiyama, Y., Yamamoto, M., Maeda, H. and Mizumoto, K. Halothane inhibition of acetylcholine-induced relaxation in rat mesenteric artery and aorta. Can. J. Anaesth. 1997, 44, 1196-1203
  14. Ito, S., Suzuki, S. and Itoh, T. Effects of a watersoluble forskolin derivative (NKH477) and a membranepermeable cyclic AMP analogue on noradrenalineinduced $Ca^{2+}$ mobilization in smooth muscle of rabbit mesenteric artery. Br. J. Pharmacol. 1993, 110, 1117-1125
  15. Itoh, T., Kanmura, Y. and Kuriyama, H. A23187 increases calcium permiability of store sites more than of surface membrane in the rabbit mesenteric artery. J.Physiol. 1985, 359, 467-484
  16. Jaiswal, N., Lambrecht, G., Mutschler, E., Tacke, R. and Malik, K. U. Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta. J. Pharmacol. Exp. Ther. 1991, 258, 842-850
  17. Kang, H. S., Choi, C. H. and Kim, J. S. Vasorelaxant properties of cyclic nucleotide phosphodiesterase inhibitors in rat aorta. Korean J. Vet. Res. 2003, 43,615-624
  18. Kamitani, K., Yamazaki, M., Yukitaka, M., Ito, Y. and Momose, Y. Effects of propofol on isolated rabbit mesenteric arteries and veins. Br. J. Anaesth. 1995, 75, 457-461
  19. Katsuki, S., Arnold, W., Mittal, C. and Murad, F. Stimulation of guanylate cyclases by sodium nitroprusside, nitroglycerine and nitric oxide in varioustissue preparation and comparison to the effects of sodium azide and hydroxyl amine. J. Cyclic Nucleotide Protein Phosphor. Res. 1977, 3, 23-35
  20. Kay, B. and Rolly, G. ICI 25868, a new intravenous induction agent. Acta. Anaesthesiol. Nelg. 1977, 28, 303-316
  21. Komas, N., Lugnier, C. and Stoclet, J. C. Endothelium-dependent and independent relaxation of the rat aorta by cyclic nucleotide phosphodiesteraseinhibitors. Br. J. Pharmacol. 1991, 104, 495-503
  22. Kurokawa, H., Murray, P. A. and Damron, D. S. Propofol attenuates β-adrenoreceptor-mediated signal transduction via a protein kinase C-dependent pathway in cardiomyocytes. Anesthesiology. 2002, 96, 688-698
  23. Langley, M. S. and Heel, R. C. Propofol - a review of its pharmacokinetic properties and use as an intravenous anesthetic. Drugs. 1988, 35, 334-372
  24. Lugnier, C., Schoeffter, P., Le Bec, A., Strouthou, E. and Stoclet, J. C. Selective inhibition of cyclic nucleotide phosphodiesterases of human, bovine and rataorta. Biochem. Pharmacol. 1986, 35, 1743-1751
  25. Miyawaki, I., Nakamura, K., Terasako, K., Toda, H., Kakuyama, M. and Mori, K. Modification of endothelium-dependent relaxation by propofol, ketamine,and midazolam. Anesth. Analg. 1995, 81, 474-479
  26. Murad, F. Cyclic guanosine monophosphate as a mediator of vasodilation. J. Clin. Invest. 1986, 78, 1-6
  27. Nagase, Y., Kaibara, M., Uezono, Y., Izumi, F., Sumikawa, K. and Taniyama, K. Propofol inhibits muscarinic acetylcholine-mediated signal transductionin Xenopus oocyte expressing the rat M1 receptor. Jpn. J. Pharmacol. 1999, 79, 319-325
  28. Nicholson, C. D., Challiss, R. A. and Shahid, M. Differential modulation of tissue function and therapeutic potential of selective inhibitors of cyclic nucleotide phosphodiesterase isoenzymes. Trends Pharmacol. Sci. 1991, 12, 19-27
  29. Park, K. W., Dai, H. B., Lowenstein, E. and Sellke, F. W. Propofol-associated dilation of rat distal coronary arteries is mediated by multiple substances, including endothelium-derived nitric oxide. Anesth. Analg. 1995, 81, 1191-1196
  30. Palmer, R. M., Ferrige, A. G. and Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1980, 327,542-546
  31. Petros, A. J., Bogle, R. G. and Pearson, J. D. Propofol stimulates nitric oxide release from cultured porcine aortic endothelial cells. Br. J. Pharmacol. 1993,109, 6-7
  32. Robinson, B. H., Ebert, T. J. and O'Brien, T. J. Mechanisms whereby propofol mediates peripheral vasodilation in humans: sympathoinhibition or directvascular relaxation? Anethesiology. 1997, 86, 64-72
  33. Rossi, M. A., Chan, C. K., Christensen, J. D., DeGuzman, E. J. and Durieux, M. E. Interaction between propofol and lipid mediator receptor: inhibition of lysophosphatidate signaling. Anesth. Analg. 1996, 83, 1090-1096
  34. Sebel, P. S. and Lowdon, J. D. Propofol: a new intravenous anesthetic. Anesthesiology. 1989, 71, 260-277
  35. Sharma, N. R. and Davis, M. J. Substance P-induced calcium entry in endothelial cells is secondary to depletion of intracellular stores. Am. J. Physiol. 1995, 268, H962-H973
  36. Taira, N. Inotropic agents: new positive inotropic agents and their mechanism of action. In: Rand, M. J., Raper, C. (EDs.) Pharmacology. pp. 477-480, Elsevier.Amsterdam, 1987
  37. Tomkinson, A. and Raeburn, D. The effect of isoenzyme-selective PDE inhibitors on methacholineinduced contraction of guinea-pig and rat ileum. Br. J.Pharmacol. 1996, 118, 2131-2139
  38. van der Zypp, A., Rechtman, M. and Majewski, H. The role of cyclic nucleotides and calcium in the relaxation produced by amrinone in rat aorta. Gen. Pharmacol. 2000, 34, 245-253
  39. Wallerstedt, S. M., Tornebrandt, K. and Bodelsson, M. Relaxant effects of propofol on human omental arteries and veins. Br. J. Anaesth. 1998, 80, 655-659
  40. Xuan, Y. T. and Glass, P. S. Propofol regulation of calcium entry pathway in cultured A10 and rat aortic smooth muscle cells. Br. J. Pharmacol. 1996, 117, 5-12