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Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus

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Abstract

Vascular smooth muscle contractile responses to neuropeptide Y, α,ß-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endotheliumin vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1–1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or α,ß-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 ± 14.0%,p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 ± 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.

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References

  1. Lundberg JM, Terenius L, Hökfelt Tet al. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function.Acta Physiol Scand 1982;116: 477–480.

    Article  CAS  PubMed  Google Scholar 

  2. Bumstock G. Overview: purinergic mechanisms.Ann NY Acad Sci 1990;603: 1–17.

    Article  Google Scholar 

  3. Edvinsson L, Håkanson R, Wahlestedt C, Uddman R. Effects of neuropeptide Y on the cardiovascular system.Trends Pharmacol Sci 1987;8: 231–235.

    Article  CAS  Google Scholar 

  4. Lundberg JM, Torsell L, Sollevi Aet al. Neuropeptide Y and sympathetic vascular control in man.Regul Pept 1985;13: 41–52.

    Article  CAS  PubMed  Google Scholar 

  5. Sundkvist G, Bramnert M, Bergström B, Manhem P, Lilja B, Ahrén B. Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction.Diabetes Res Clin Pract 1992;15: 219–226.

    Article  CAS  PubMed  Google Scholar 

  6. Andersson D, Brunkwall J, Bergqvist D, Edvinsson L. Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits.J Autonom Nerv Syst 1992;37: 215–222.

    Article  CAS  Google Scholar 

  7. Andersson D, Brunkwall J, Bergqvist D, Wahlestedt C, Edvinsson L. Reduced contractile responses to neuropeptide Y but unchanged to endothelin-1 of arteries from diabetic rabbits: a Gi/Go-coupled effect? Neuropeptides in normal and pathological function.Neuropeptides 1992;22: 1.

    Google Scholar 

  8. P2 purinoceptors. Receptor and ion channel nomenclature supplement.Trends Pharmacol Sci 1994;15 (3): 38.

    Google Scholar 

  9. Gawler D, Milligan G, Spiegel AM, Unson CG, Housley MD. Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes.Nature 1987;327: 229–232.

    Article  CAS  PubMed  Google Scholar 

  10. Strassheim D, Milligan G, Houslay MD. Diabetes abolishes the GTP-dependent, but not the receptor-dependent inhibitory function of the inhibitory guanine-nucleotide-binding regulatory protein (Gi) on adipocyte adenylate cyclase activity.Biochem J 1990;266: 521–526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Högestedt ED, Andersson KE, Edvinsson L. Mechanical properties of rat cerebral arteries as studied by a sensitive device for recording of mechanical activity in isolated small blood vessels.Acta Physiol Scand 1983;117: 49–61.

    Article  Google Scholar 

  12. Angus JA, Lew MJ. Interpretation of the acetylcholine test of endothelial cell dysfunction in hypertension.J Hypertens 1992;10 (7): 179–186.

    Google Scholar 

  13. Högestedt ED, Andersson KE. Mechanisms behind the biphasic contractile response to potassium depolarization in isolated rat cerebral arteries.J Pharmacol Exp Ther 1984;228: 187–195.

    Google Scholar 

  14. Sjögren A, Edvinsson L. Vasomotor changes in isolated coronary arteries from diabetic rats.Acta Physiol Scand 1988;134: 429–436.

    Article  PubMed  Google Scholar 

  15. Agrawal DK, Bhimji S, McNeill JH. Effect of chronic experimental diabetes on vascular smooth muscle function in rabbit carotid artery.J Cardiovasc Pharmacol 1987;9: 584–593.

    Article  CAS  PubMed  Google Scholar 

  16. McLeod KM, McNeill JH. The influence of chronic diabetes on contractile responses of rat isolated blood vessels.Can J Physiol Pharmacol 1984;63: 52–57.

    Article  Google Scholar 

  17. Head RJ, Longhurst PA, Panek RL, Stitzel RE. A contrasting effect of the diabetic state upon the contractile responses of aortic preparations from the rat and rabbit.Br J Pharmacol 1987;91: 275–286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Longhurst PA, Head RJ. Responses of isolated perfused mesenteric vasculature from diabetic rats: The significance of appropriate control tissues.J Pharmacol Exp Ther 1985;235 (1): 45–49.

    CAS  PubMed  Google Scholar 

  19. Sullivan S, Sparks HV. Diminished contractile response of aortas from diabetic rabbits.Am J Physiol 1979;236 (2): H301-H306.

    CAS  PubMed  Google Scholar 

  20. Dunbar JC, Ergene E, Anderson GF, Barraco RA. Decreased cardiorespiratory effects of neuropeptide Y in the nucleus tractus solitarius in diabetes.Am J Physiol 1992;262: R865-R871.

    CAS  PubMed  Google Scholar 

  21. Abebe W, Harris KH, McLeod KM. Enhanced contractile responses of arteries from diabetic rats to alpha1-adrenoceptor stimulation in the absence and presence of extracellular calcium.J Cardiovasc Pharmacol 1990;16: 239–248.

    Article  CAS  PubMed  Google Scholar 

  22. Cohen RA, Tesfamariam B, Weisbrod RM, Zitnay KM. Adrenergic denervation in rabbits with diabetes mellitus.Am J Physiol 1990;259 (28): H55-H61.

    CAS  PubMed  Google Scholar 

  23. Koltai MZ, Rösen P, Ballagy-Pordany G, Hadhazy P, Pogatsa G. Increased vasoconstrictor response to noradrenaline in femoral vascular bed of diabetic dogs. Is thromboxane A2 involved?Cardiovasc Res 1990;24: 707–710.

    Article  CAS  PubMed  Google Scholar 

  24. Morff RJ. Microvascular reactivity to norepinephrine at different arteriolar levels and durations of streptozocin-induced diabetes.Diabetes 1990;39: 354–360.

    Article  CAS  PubMed  Google Scholar 

  25. Harris KH, MacLeod KM. Influence of the endothelium on contractile responses of arteries from diabetic rats.Eur J Pharmacol 1988;153: 55–64.

    Article  CAS  PubMed  Google Scholar 

  26. Abiru T, Kamata K, Kasuya Y. Effects of chronic diabetes on vascular responses of basilar artery and aorta from rabbits with alloxaninduced diabetes.Res Commun Chem Pathol Pharmacol 1991;74 (1), 71–87.

    CAS  PubMed  Google Scholar 

  27. Turlapaty PMV, Lum G, Altura BM. Vascular responses and serum biochemical parameters in alloxan diabetes mellitus.Am J Physiol 1980;239: E412-E421.

    CAS  PubMed  Google Scholar 

  28. Fulton DJR, Hodgson WC, Sikorski BW, King RG. Attenuated responses to endothelin-1, KCl and CaCl2, but not noradrenaline, of aortae from rats with streptozotocin-induced diabetes mellitus.Br J Pharmacol 1991;104: 928–932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bodmer CW, Patrick AW, Hoe TV, Williams G. Exaggerated sensitivity to NE-induced vasoconstriction in IDDM patients with microalbuminuria.Diabetes 1992;41: 209–214.

    Article  CAS  PubMed  Google Scholar 

  30. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.Nature 1980;288: 373–376.

    Article  CAS  PubMed  Google Scholar 

  31. Garcia MJ, McNamara PM, Gordon T, Kannel WB. Morbidity and mortality in diabetics in the Framingham population.Diabetes 1974;23: 105–111.

    Article  CAS  PubMed  Google Scholar 

  32. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study.JAMA 1979;241: 2035–2038.

    Article  CAS  PubMed  Google Scholar 

  33. Christlieb AR. Diabetes and cardiovascular disease. Mechanisms and treatment.Am J Cardiol 1973;32: 595–606.

    Article  Google Scholar 

  34. Ellenberg M. Diabetic autonomic neuropathy: role in vascular events.N Y State J Med 1978;78: 2214–2218.

    CAS  PubMed  Google Scholar 

  35. Edmonds ME, Nicolaides KH, Watkins PJ. Autonomic neuropathy and foot ulceration.Diabet Med 1986;3: 56–59.

    Article  CAS  PubMed  Google Scholar 

  36. Levy DM, Karanth SS, Springall DR, Polak JM. Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study.Diabetologia 1989;32: 427–433.

    Article  CAS  PubMed  Google Scholar 

  37. Schmidt RE, Spencer SA, Coleman BD, Roth KA. Immunohistochemical localization of GAP-43 in rat and human sympathetic nervous system — effects of aging and diabetes.Brain Res 1991;552: 190–197.

    Article  CAS  PubMed  Google Scholar 

  38. Schmidt RE, Dorsey DE, Roth KA. Immunohistochemical characterization of NPY and substance P containing nerve terminals in aged and diabetic human sympathetic ganglia.Brain Res 1992;583: 320–326.

    Article  CAS  PubMed  Google Scholar 

  39. Winqvist RJ, Bevan JA. The effect of surgical sympathetic denervation upon the development of intrinsic myogenic tone and the alpha and beta adrenergic receptor-mediated responses of the rabbit facial vein.J Pharmacol Exp Ther 1979;211: 1–6.

    Google Scholar 

  40. Edvinsson L, Copeland JR, Emson PC, McCulloch J, Uddman R. Nerve fibers containing neuropeptide Y in the cerebrovascular bed: immunocytochemistry, radioimmunoassay and vasomotor effects.J Cereb Blood Flow Metab 1987;7: 45–57.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Vascular Research, Department of Internal Medicine, Lund University, Sweden

    H. Lind MD, D. Erlinge MD PhD & L. Edvinsson MD

  2. Health Sciences Centre, Lund University, Helgeandsg 16, S-223 54, Lund, Sweden

    H. Lind MD

  3. Department of Surgery, Malmö General Hospital, Sweden

    J. Brunkwall MD PhD

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  1. H. Lind MD
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  2. D. Erlinge MD PhD
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  3. J. Brunkwall MD PhD
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  4. L. Edvinsson MD
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Lind, H., Erlinge, D., Brunkwall, J. et al. Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus. Clinical Autonomic Research 5, 191–197 (1995). https://doi.org/10.1007/BF01824006

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