Mechanism of vasodilatation induced by substance P in isolated rabbit renal artery

토끼 적출 신동맥에 있어서 substance P에 의한 이완작용 기전

  • Kim, Joo-heon (College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University) ;
  • Jeon, Seok-cheol (Cardiac center Masan Samsung General Hospital) ;
  • Hong, Yonggeun (Department of Internal Medicine-Cardiology, University of Texas Southwestern Medical Center at Dallas)
  • Accepted : 2003.11.20
  • Published : 2003.12.25

Abstract

The effects of removing the endothelium on the vasodilatory response to substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) was examined in the isolated rabbit renal artery. The vasodilator response to substance P ($0.1{\mu}M$) was completely absent in vessels in which the endothelium had previously been removed. There was no significant difference in the vasodilatation produced in response to CGRP ($0.1{\mu}M$), or VIP ($0.1{\mu}M$) in the intact and removed-endothelium rabbit renal artery segments. L-NAME ($100{\mu}M$) significantly reduced the vasodilatory response to substance P ($0.1{\mu}M$). This inhibition was significantly attenuated when L-arginine (10 mM) was also present in the organ bath along with L-NAME ($100{\mu}M$). Indomethacin ($1{\mu}M$) did not significantly affect the vasodilatation produced in response to substance P ($0.1{\mu}M$). The inhibitory effect of L-NAME ($100{\mu}M$) and indomethacin ($1{\mu}M$) on the vasodilatory response to substance P ($0.1{\mu}M$) was not significantly different from that produced by L-NAME ($100{\mu}M$) alone. This study indicates that substance P induced vasodilatation via an endothelium-dependent mechanism in the isolated rabbit renal artery. It also established that CGRP and VIP induced vasodilatation by an endothelium-independent mechanism and substance P-induced vasodilatation is at least partially via NO.

Keywords

References

  1. Angus, J. A. and Cocks, T. M. Endothelium-derived relaxing factor. Pharmacvol Ther, 1989, 41, 303-352
  2. Beny, J. L. and Brunet, P. C. Electrophysiological and mechanical effects of substance P and acetylcholine on rabbit aorta. J. Physiol (London), 1988, 398, 277-289
  3. Beny, J. L., Brunet, P. C. and Huggel, H. Effect of mechanical stimulation, substance P and vasoactive intestinal pulypeptide on the electrical and mechanical activities of circular smooth muscle from pig coronary arteries contracted with acetylcholine: role of endothelium. Pharmacology, 1986. 33, 61-68
  4. Boulanger, C., Hendrickson, H., Lorenz, R. R. and Vanhoutte, P. M. Release of different relaxing factors by cultured porcine endothelial cells. Circ. Res. 1989, 64, 1070-1078
  5. Brizzolara, A. L. and Burnstock, G. Endothelium-dependent and endothelum-independent vasodilatation of the hepatic artery of the rabbit. Brit. J. Pharmacol. 1991. 103, 1206-1212
  6. Cherry, P. D., Furchgott, R. W., Zawadzki, J. V., Jothianandan, Role of endothelial cells in relaxation of isolated arteries by bradykinin. Proc. Natl. Sci. USA, 1982, 79, 2106-2110
  7. DeMey, J. and Vanhoutte, P. M. Removal of endothelium and arterial reactivity to acetylcholine and adenine nucleotides. Proc. Brit. Pharmacol. Soc. 10-12 Sept C.46
  8. Forstermann, U., Hertting, G. and Neufgang, B. The role of endothelial and non-endothelial prostaglandins in the relaxation of isolated blood vessels of the rabbit induced by acetylcholine and bradykinin. Brit. J. Phannacol. 1986, 87, 521-532
  9. Furchgott, R. F. Role of the endothelium in responses of vascular smooth muscle. Circ. Res. 1983, 53, 557-573
  10. Furchgott, R. F. The role of the endothelium in the responses of vascular smooth muscle to drugs. Ann. Rev. Pharmacol. Toxicol, 1984, 24, 175-197
  11. Furchgott, R. F., Khan, M. T, Joithianandan, D., Evidence supporting the proposal that endothelium- derived relaxing factor is nitric oxide. Thrombosis Res. Suppl. 1987, VII 5
  12. Furchgott, R. F. and Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980, 288, 373-376
  13. Herbaczynska-Cegro, K. and Vane, J. R. Contribution of intrarenal generation of prostaglandins to autoreeulation of renal blood flow in the dog. Circ. Res. 1973, 32, 428-436
  14. Ignarro, L. J., Byrns, R. E., Buga, G. M. and Wood, K. S. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ. Res. 1987, 61, 866-879
  15. Ignarro, L. J., Wood, K. S. and Byrns, R. E. Pharmacological and biochemical properties of EDRF: evidence that EDRF is closely related to nitric oxide (NO) radical, Circulation, 1986, 74, 287-299
  16. Kim, J. H., Kwun, J. K. and Kirn, Y. K. Relatiunship of action adenosine triphosphate and prostaglandin $F_2_\alpha$ on uterine smooth muscle motility in immature pig. Korean J. Physiol. 1988, 22, 31-39
  17. Kim, J. H., Shim, C. S. and Jeon, S. C. Involvement of nitric oxide and prostanuid on the endothelium- dependent vasodilatation by acetylcholine in the isolated rabbit renal artery. Korean J. Vet. Res. 2001, 41. 299-304
  18. Kitagawa, S., Yamaguchi, Y., Kunitoino, M., Sanioshima, E. and Fujiwara, M. NG-nilro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery. Life Sci. 1994, 55, 491-498
  19. Loesch, A. and Burnstock, G. Ultrastructural localisation of serotonin and substance P in vascular endothelial cells of rat femoral and mesenteric arteries. Anat. Embryol. 1988, 178, 137-142
  20. Mayer, B., Schmidt, K., Humbert, P. and Bohme, E. Biosynthesis of endothelium-derived relaxing factor: a cytosolic enzyme in porcine aortic endothelial cells $Ca^2^+$-dependently converts L-arginine into an activator of soluble guanylate cyclase. Biochem. Biophys. Res. Commun. 1989, 164, 678-685
  21. Milner, R, Kirkpatrick, K. A., Ralevic, V., Toothill, V., Pearson, J. and Burnstock, G. Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow. Proc R Soc Lond B, 1990, 241, 245-248
  22. Needham, L., Cusack, N. J., Pearson, J. D. and Gordon, J. L. Characteristics of the P2-purinoceptor that mediates prostacyclin production by pig aortic endothelial cells. Eur. J. Pharmacol. 1987, 134, 199-209
  23. Palmer, R. M., Ferridge, A. G. and Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 1987, 327, 524-526
  24. Palmer, R. M. and Moncada, S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem. Biophys. Res. Commun. 1989, 158, 348-352
  25. Palmer, R. M., Rees, D. D., Ashton, D. S. and Moncada, S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 1988, 153, 1251-1256
  26. Peach, M. J., Loeb, A. L., Singer, H. A. and Saye, J. Endothelium-derived vascular relaxing factor. Hypertension, 1985, 7, 94-100
  27. Peach, M. J., Singer, H. A. and Loeb, A. L. Mechanisms of endothelium-dependent vascular smooth muscle relaxation. Biochem. Pharmacol. 1985, 34, 1867-1874
  28. Radomski, M. W., Palmer, R. M. and Moncada, S. The antiaggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Brit. J. Pharmacol. 1987, 92, 639-646
  29. Ralevis, V., Milner, R, Hiidlicka. 0., Kristek, F. and Burnstock, G. Substance P is release from the endothelium of normal and capsaicin treated rat hindlimb vasculature in vivo by increased flow. Circ. Res. 1990, 66, 1178-1183
  30. Rees, D. D., Palmer, R. M., Schulz, R., Hodson, H. F. and Moncada, S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Brit. J. Pharmacol. 1990, 101, 746-752
  31. Schmidt, H. W., Klein, M. M., Niroomand, F. and Bohme, E. Is arginine a physiological precursor of endothelium-derived nitirc oxide? Eur. J. Pharmacol. 1988, 148, 293-295
  32. Vane, J. R. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin like drugs. Nat. New Biol. 1971, 231, 232-235
  33. Vanhoutte, P. M. and Rimele. T. J. Role of the endothelium in the control of vascular smooth muscle function. J. Physiol. 1982-1983, 78, 681-686