Induces Vasodilatation of Rat Mesenteric Artery in vitro Mainly by Inhibiting Receptor-Mediated $Ca^{2+}$ -Influx and $Ca^{2+}$ -Release

  • Cao Yong-Xiao (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Division of Experimental Vascular Research, Department of Medicine, Lund University) ;
  • Zheng Jian-Pu (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education) ;
  • He Jian-Yu (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education) ;
  • Li Jie (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education) ;
  • Xu Cang-Bao (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Division of Experimental Vascular Research, Department of Medicine, Lund University) ;
  • Edvinsson Lars (Department of Pharmacology, Medical School of Xi'an Jiaotong University, and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Division of Experimental Vascular Research, Department of Medicine, Lund University)
  • Published : 2005.06.01

Abstract

The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1$\mu$M, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the ${\alpha}_1$-adrenoreceptor. The $\beta$-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and $CaCl_2$ in $Ca^{2+}$-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular $Ca^{2+}$ influx through the receptor-operated calcium channels and intracellular $Ca^{2+}$ release from the $Ca^{2+}$ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular $Ca^{2+}$ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated $Ca^{2+}$-influx and $Ca^{2+}$-release, and partly from the endothelium mediated by EDHF.

Keywords

References

  1. Alm, R., Edvinsson, L., and Malmsjo, M., Organ culture: a new model for vascular endothelium dysfunction. BMC Cardiovasc. Disord., 2, 8-12 (2002) https://doi.org/10.1186/1471-2261-2-8
  2. Broekaert, A. and Godfraind, T., A comparison of the inhibitory effect of cinnarizine and papaverine on the noradrenalin and calcium evoked contraction of isolated rabbit aorta and mesenteric arteries. Eur. J. Pharmacol., 53, 281-288 (1979) https://doi.org/10.1016/0014-2999(79)90134-1
  3. Brown, J. H. and Taylor, P., Muscarinic agonists and antagonists. In: Hardman J, Limbird LE, Gilman AG, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw-Hill; p162- 171, (2001)
  4. Cao, Y. X., He, L. C., Xu, C. B., and Edvinsson, L., Alteration in contractile response to noradrenaline, 5-hydroxytryptamine, sarafotoxin 6c, and angiotensin II in rat mesenteric artery during organ culture. Acad. J. XJTU.,16,155-159 (2004)
  5. Chang, K. C. and Hahn, K. H., Is $\alpha$-adrenoceptor blockade responsible for atropine flush? Eur. J. Pharmacol., 284, 331-334 (1995) https://doi.org/10.1016/0014-2999(95)00484-3
  6. Chen, H. H., Large dose atropine alkaloids in the treatment of shock. Resuscitation, 10, 149-151 (1983) https://doi.org/10.1016/0300-9572(83)90001-1
  7. Choi, Y. D., Chung, W. S., and Choi, H. K., The action mechanism of relaxation effect of atropine on the isolated rabbit corpus cavernosum. J. Urol., 161, 1976-199 (1999) https://doi.org/10.1016/S0022-5347(05)68867-2
  8. Doughty, J. M., Plane, F. and Langton, P. D., Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium. Am. J. Physiol., 276, H1107-1112 (1999)
  9. Furchgott, R. F. and Zawadzki, J. V., The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 288, 373-376 (1980) https://doi.org/10.1038/288373a0
  10. Hall, S., Honig, S. C., Payton, T. R., Krane, R. J., and Goldstein, I., Use of atropine sulfate in pharmacologic erections:initial experience with one year follow-up in the United States. J. Urol., 147, 265-269 (1992)
  11. Hanghighi, K. M., Pollock, D., and Fallah, H. H., Vasorelaxant effects of atropine: role of nitric oxide/endothelium derived relaxing factor. Indial. J. Pharmacol., 34, 244-255 (2002)
  12. Jiang, Q. S., Huang, X. N., Sun, A. S., Wu, Q., and Xie, X. L., Effect of isocorydine on $Ca^{2+}$ influx and $Ca^{2+}$ release in rabbit aortic smooth muscle. Chin. Pharmacol. Bull., 14, 546-548 (1998)
  13. Jin, M. W. and Zhou, Z. Y., The treatment of shock by combining Chinese traditional medicine and Western medicine. Zhejing J ITCWM, 14, 397-399 (2004)
  14. Leijten, P. A. and Van Breemen, C., The effects of caffeine on the noradrenaline-sensitive calcium store in rabbit aorta. J. Physiol. 1984, 357, 327-339 https://doi.org/10.1113/jphysiol.1984.sp015502
  15. Liu, S. Q., Zang, W. J., Li, Z. L., Yu, X. J., and Li, B. P., Effect of atropine on denervated rabbit ear blood vessels. J. Cardiovasc. Pharmacol., 43, 99-105 (2004) https://doi.org/10.1097/00005344-200401000-00015
  16. Moncada, S., Palmer, R. M., and Higgs, E. A., Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev., 43,109-142 (1991)
  17. Qian, J. P., Treatmeat of 13 patients suffering from shock with atropine and naloxone. Acta Academiae Medicinae Suzhou., 19, 75-76 (1999)
  18. Tijen, K., Sinan, G., Baris, K., Bulent, S., Haluk, K., and Ahmet, S. S., High-concentration tramdol-induced vasodilation in rabbit aorta is mediated by both endothelium-dependent and -in- dependent mechanisms. Acta Pharmacol. Sin., 24, 385-389 (2003)
  19. Xu, F. M., The salvage of 26 children suffering from serious infected shock with henbane drugs. Zhejing Practical Medicine, 2, 43-45 (1997)