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Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses.

Abstract: The objective of this study was to determine and compare the in vitro responses of equine large colon arterial and venous rings to vasodilatory neuropeptides; calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium-dependent vasodilator. Responses of vessel rings to graded concentrations (10(-11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded, and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that were pre-contracted with norepinephrine. Percentage maximal relaxation (PMR), defined as the % decrease from the contracted state, was determined. Because all rings did not relax at least 50%, EC50 values could not be consistently calculated. Arterial rings with intact endothelium were more sensitive to CGRP, compared with VIP and SP, and venous rings of all conditions were more sensitive to VIP than CGRP or SP. Overall, arteries had a greater PMR for ACh compared with SP and VIP. Intact and L-NAME treated arteries had a greater PMR than denuded arteries; there were no differences in PMR of intact and L-NAME treated arteries. Veins had a greater PMR for VIP than CGRP, SP, or ACh. Calcitonin gene-related peptide caused greater relaxation in intact arteries, whereas VIP causes greater relaxation in veins. Arterial relaxation was dependent upon the presence of intact endothelium. The response of veins to VIP among the conditions tested was not different, suggesting VIP has direct actions on venous smooth muscle. These neuropeptides modulate vasomotor tone via vasorelaxation in colonic arteries and veins.
Publication Date: 2005-06-24 PubMed ID: 15971675PubMed Central: PMC1142178
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research investigates how equine colonic arterial and venous rings respond to various vasodilatory neuropeptides. It further examines the role of endothelium and nitric oxide in this process.

Research Parameters and Methodology

  • The study aimed to analyze and compare in vitro responses of equine large colon arterial and venous rings to different vasodilatory neuropeptides. These included the calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh).
  • Responses to different drug concentrations were tested in endothelium-intact, denuded, and L-NAME (Nω-nitro-L-arginine methyl ester)-treated rings pre-contracted with norepinephrine.
  • The research used Percentage Maximal Relaxation (PMR) as a measure to determine relaxation. PMR is defined as the percentage decrease from the pre-contracted state.

Key Findings

  • The study found that arterial rings with intact endothelium were more sensitive to CGRP compared to VIP and SP. Venous rings, meanwhile, were more sensitive to VIP than either CGRP or SP.
  • The arteries had a greater PMR with ACh compared to SP and VIP. Moreover, the intact and L-NAME-treated arteries showed a greater PMR compared to the denuded arteries.
  • In terms of venous responses, veins had a greater PMR for VIP than for CGRP, SP, or ACh. VIP caused a greater relaxation reaction in veins, while CGRP was more effective in intact arteries.
  • It was concluded that arterial relaxation is dependent on the presence of intact endothelium. However, the differences in venous responses to VIP did not significantly vary among the conditions tested, implying that VIP has a direct impact on the venous smooth muscle.

Conclusions

  • The research suggests that these neuropeptides play a role in modulating vasomotor tone via vasorelaxation in colonic arteries and veins.
  • The findings can provide valuable insights into understanding equine vascular physiology and may help in developing new treatment strategies for equine colonic disorders.

Cite This Article

APA
Moore RM, Sedrish SA, Holmes EP, Koch CE, Venugopal CS. (2005). Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses. Can J Vet Res, 69(2), 116-122.

Publication

ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 69
Issue: 2
Pages: 116-122

Researcher Affiliations

Moore, Rustin M
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA. rmoore@vetmed.lsu.edu
Sedrish, Steven A
    Holmes, Earnestine P
      Koch, Catherine E
        Venugopal, Changaram S

          MeSH Terms

          • Acetylcholine / pharmacology
          • Animals
          • Arteries / drug effects
          • Calcitonin Gene-Related Peptide / pharmacology
          • Colon / blood supply
          • Colon / drug effects
          • Colon / metabolism
          • Dose-Response Relationship, Drug
          • Endothelium, Vascular / drug effects
          • Endothelium, Vascular / metabolism
          • Endothelium, Vascular / physiology
          • Horses
          • In Vitro Techniques
          • Muscle Contraction
          • Neuropeptides / pharmacology
          • Nitric Oxide / metabolism
          • Nitric Oxide / physiology
          • Norepinephrine / pharmacology
          • Substance P / pharmacology
          • Vasoactive Intestinal Peptide / pharmacology
          • Vasodilator Agents / pharmacology
          • Veins / drug effects

          References

          This article includes 34 references
          1. Granger DN, Kvietys PR, Korthius RJ, Premen AJ. Microcirculation of the intestinal mucsoa. Handbook of Physiology. Section 6: The Gastrointestinal System 1989:1405–1474.
          2. Moore RM, Muir WW, Bertone AL, Beard WL. Characterization of the hemodynamic and metabolic alterations in the large colon of horses during low-flow ischemia and reperfusion.. Am J Vet Res 1994 Oct;55(10):1444-53.
            pubmed: 7998703
          3. Moore RM, Hardy J, Muir WW. Mural blood flow distribution in the large colon of horses during low-flow ischemia and reperfusion.. Am J Vet Res 1995 Jun;56(6):812-8.
            pubmed: 7653893
          4. Moore RM, Bertone AL, Muir WW, Stromberg PC, Beard WL. Histopathologic evidence of reperfusion injury in the large colon of horses after low-flow ischemia.. Am J Vet Res 1994 Oct;55(10):1434-43.
            pubmed: 7998702
          5. Provost PJ, Stick JA, Patterson JS, Hauptman JG, Robinson NE, Roth R. Effects of heparin treatment on colonic torsion-associated hemodynamic and plasma eicosanoid changes in anesthetized ponies.. Am J Vet Res 1991 Feb;52(2):289-97.
            pubmed: 2012340
          6. Palombo JD, Blackburn GL, Forse RA. Endothelial cell factors and response to injury.. Surg Gynecol Obstet 1991 Dec;173(6):505-18.
            pubmed: 1948614
          7. Vanhoutte PM, Rubanyi GM, Miller VM, Houston DS. Modulation of vascular smooth muscle contraction by the endothelium.. Annu Rev Physiol 1986;48:307-20.
          8. Moncada S, Higgs EA. Endogenous nitric oxide: physiology, pathology and clinical relevance.. Eur J Clin Invest 1991 Aug;21(4):361-74.
          9. Henninger DD, Snyder JR, Pascoe JR, Dilling GW. Microvascular permeability changes in ischemia/reperfusion injury in the ascending colon of horses.. J Am Vet Med Assoc 1992 Oct 15;201(8):1191-6.
            pubmed: 1429157
          10. Lüscher TF, Cooke JP, Houston DS, Neves RJ, Vanhoutte PM. Endothelium-dependent relaxations in human arteries.. Mayo Clin Proc 1987 Jul;62(7):601-6.
            pubmed: 3473272doi: 10.1016/s0025-6196(12)62299-xgoogle scholar: lookup
          11. Baxter GM. Alterations of endothelium-dependent digital vascular responses in horses given low-dose endotoxin.. Vet Surg 1995 Mar-Apr;24(2):87-96.
          12. Dockray GJ. Physiology of enteric neuropeptides. 2nd ed. New York: Raven Press, 1987.
          13. Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator.. Nature 1985 Jan 3-9;313(5997):54-6.
            pubmed: 3917554doi: 10.1038/313054a0google scholar: lookup
          14. Burns GA, Cummings JF. Neuropeptide distributions in the colon, cecum, and jejunum of the horse.. Anat Rec 1993 Jun;236(2):341-50.
            pubmed: 7687832doi: 10.1002/ar.1092360207google scholar: lookup
          15. Fehér E, Burnstock G. Ultrastructural localisation of substance P, vasoactive intestinal polypeptide, somatostatin and neuropeptide Y immunoreactivity in perivascular nerve plexuses of the gut.. Blood Vessels 1986;23(3):125-36.
            pubmed: 2424525doi: 10.1159/000158629google scholar: lookup
          16. Furchgott RF, Vanhoutte PM. Endothelium-derived relaxing and contracting factors.. FASEB J 1989 Jul;3(9):2007-18.
            pubmed: 2545495
          17. Leister I, Mbachu EM, Post S, Samel ST, Stojanovic T, Gutt CN, Becker H, Markus PM. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate hepatic microvasculatory disturbances following intestinal ischemia and reperfusion.. Digestion 2002;66(3):186-92.
            pubmed: 12481165doi: 10.1159/000066761google scholar: lookup
          18. Roudenok V, Gutjar L, Antipova V, Rogov Y. Expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide in human stellate ganglia after acute myocardial infarction.. Ann Anat 2001 Jul;183(4):341-4.
            pubmed: 11508359doi: 10.1016/s0940-9602(01)80176-xgoogle scholar: lookup
          19. Moore RM, Charalambous AC, Masty J. Alterations in colonic arterial and venous plasma neuropeptide concentrations in horses during low-flow ischemia and reperfusion of the large colon.. Am J Vet Res 1996 Aug;57(8):1200-5.
            pubmed: 8836375
          20. Venugopalan CS, Moore RM, Holmes EP, Sedrish SA, Koch CE. Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators.. J Auton Pharmacol 1998 Aug;18(4):231-7.
          21. Vanhoutte PM, Miller VM. Heterogeneity of endothelium-dependent responses in mammalian blood vessels.. J Cardiovasc Pharmacol 1985;7 Suppl 3:S12-23.
          22. Goodman EC, Iversen LL. Calcitonin gene-related peptide: novel neuropeptide.. Life Sci 1986 Jun 16;38(24):2169-78.
            pubmed: 2423836doi: 10.1016/0024-3205(86)90568-0google scholar: lookup
          23. Gates TS, Zimmerman RP, Mantyh CR, Vigna SR, Mantyh PW. Calcitonin gene-related peptide-alpha receptor binding sites in the gastrointestinal tract.. Neuroscience 1989;31(3):757-70.
            pubmed: 2556661doi: 10.1016/0306-4522(89)90439-9google scholar: lookup
          24. Kawasaki H, Takasaki K, Saito A, Goto K. Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat.. Nature 1988 Sep 8;335(6186):164-7.
            pubmed: 2901042doi: 10.1038/335164a0google scholar: lookup
          25. Holzer P, Lippe IT, Jocic M, Wachter C, Erb R, Heinemann A. Nitric oxide-dependent and -independent hyperaemia due to calcitonin gene-related peptide in the rat stomach.. Br J Pharmacol 1993 Sep;110(1):404-10.
          26. Bateson PG, Buchanan KD, Stewart DM, Parks TG. The release of vasoactive intestinal peptide during altered mid-gut blood flow.. Br J Surg 1980 Feb;67(2):131-4.
            pubmed: 7362944doi: 10.1002/bjs.1800670219google scholar: lookup
          27. Somjen G, Fletcher DR, Shulkes A, Hardy KJ. Experimental mesenteric ischaemia in sheep: gut peptide release and haemodynamic changes.. J Gastroenterol Hepatol 1989 May-Jun;4(3):251-8.
          28. Eklund S, Jodal M, Lundgren O, Sjöqvist A. Effects of vasoactive intestinal polypeptide on blood flow, motility and fluid transport in the gastrointestinal tract of the cat.. Acta Physiol Scand 1979 Apr;105(4):461-8.
          29. Hallberg D, Pernow B. Effect of substance P on various vascular beds in the dog.. Acta Physiol Scand 1975 Feb;93(2):277-85.
          30. Cogswell AM, Johnson PJ, Adams HR. Evidence for endothelium-derived relaxing factor/nitric oxide in equine digital arteries.. Am J Vet Res 1995 Dec;56(12):1637-41.
            pubmed: 8599526
          31. Lincoln TM, Cornwell TL, Komalavilas P. The nitric oxidecyclic GMP signaling system. Biochemistry of smooth muscle contraction 1996:257–268.
          32. Guyton AC. Overview of the circulation, and medical physics of pressure, flow, and resistance. Textbook of Medical Physiology 8th ed. 1991:150–158.
          33. Guyton AC. The microcirculation and the lymphatic system: Capillary fluid exchange, interstitial fluid, and lymph flow. The Textbook of Medical Physiology 8th ed. 1991:170–184.
          34. Dabareiner RM, Snyder JR, White NA, Pascoe JR, Harmon FA, Gardner I, Woliner MJ, Pinney D, Sullins KE. Microvascular permeability and endothelial cell morphology associated with low-flow ischemia/reperfusion injury in the equine jejunum.. Am J Vet Res 1995 May;56(5):639-48.
            pubmed: 7661461

          Citations

          This article has been cited 5 times.
          1. Moro C, Phelps C. Urothelium removal does not impact mucosal activity in response to muscarinic or adrenergic receptor stimulation. Tissue Barriers 2023 Jul 3;11(3):2099214.
            doi: 10.1080/21688370.2022.2099214pubmed: 35803762google scholar: lookup
          2. Boerman EM, Segal SS. Depressed perivascular sensory innervation of mouse mesenteric arteries with advanced age. J Physiol 2016 Apr 15;594(8):2323-38.
            doi: 10.1113/JP270710pubmed: 26010764google scholar: lookup
          3. Zhang S, Liu Y, Guo S, Zhang J, Chu X, Jiang C, Zhu D. Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings through two distinct mechanisms. J Physiol Sci 2010 Nov;60(6):389-97.
            doi: 10.1007/s12576-010-0107-xpubmed: 20694540google scholar: lookup
          4. Shahbazi F, Holmgren S, Jensen J. Cod CGRP and tachykinins in coeliac artery innervation of the Atlantic cod, Gadus morhua: presence and vasoactivity. Fish Physiol Biochem 2009 Aug;35(3):369-76.
            doi: 10.1007/s10695-008-9257-7pubmed: 18836843google scholar: lookup
          5. Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM. Comparison of 2 endothelin-receptor antagonists on in vitro responses of equine palmar digital arterial and venous rings to endothelin-1. Can J Vet Res 2006 Jul;70(3):197-205.
            pubmed: 16850942