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Aging Clinical and Experimental Research

, Volume 6, Issue 4, pp 277–286 | Cite as

Vascular responses to neuropeptide Y in the rat: Effect of age

  • Thomas C. Glenn
  • S. P. Duckies
Original Article

Abstract

Neuropeptide Y(NPY) is co- released with norepinephrine (NE) from sympathetic neurons, which innervate blood vessels, and acts to potentiate NE- induced smooth muscle contraction. This study sought to determine if vascular levelsof NPY- like immunoreactivity or the contractile effects of NPY are altered by age in segments of isolated blood vessels from Fischer 344 and Brown Norway F344- F- l rats. Tissue extracts of femoral and tail arteries of Fischer 344 rats, aged 6, 12, 20, and 24 months, were analyzed for NPY content by radioimmunoassay. Neither blood vessel showed a significant age- related difference in NPY content. Contractile responses of the tail artery to adrenergic transmural nerve stimulation (TNS) were compared in the same age groups. No significant age- related differences in contractile responses to TNS were observed in either rat strain. NPY, at concentrations of 1 and 10 nM, both potentiated and prolonged the contractile response to TNS; 6- month- old F- 344 rats were significantly less responsive to the effects of NPY However, advancing age from 12 to 24 months did not alter the responses to NPY in either rat strain. We conclude that an age- dependent increase in the contractile responses to NPY occurs from age 6 to 12 months, and this responsiveness to NPY is maintained through senescence. (Aging Clin. Exp. Res. 6: 277- 286, 1994)

Keywords

Aging contraction duration cotransmission tumor vascular smooth muscle 

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References

  1. 1.
    Larhammar D., Söderberg C., Blomquist AG.: Evolution of the NPY family of peptides. In: Colmers W.F., Wahlestedt C. (Eds.), The Biology of Neuropeptide Y and Related Peptides. Humana Press, Totowa, 1993, pp. 1–28.CrossRefGoogle Scholar
  2. 2.
    Lundberg J.M., Terenius L., Hökfelt T., Goldstein M.: High levels of NPY in peripheral noradrenergic neurons in various mammals including man. Neurosci. Lett. 42: 167–172, 1983.PubMedCrossRefGoogle Scholar
  3. 3.
    Lundberg J.M., Änggård A., Theodorsson-Norheim E., Pernow J.: Guanethidine-sensitive release of NPY-like immunoreactivity in the cat spleen by sympathetic nerve stimulation. Neurosci. Lett. 52: 175–180, 1984.PubMedCrossRefGoogle Scholar
  4. 4.
    Zukowska-Grojec Z., Wahlestedt C.: Origins and actions of NPY in the cardiovascular system. In: Colmers W.F., Wahlestedt C. (Eds.), The Biology of Neuropeptide Y and Related Peptides. Humana Press, Totowa, 1993, pp. 315–372.CrossRefGoogle Scholar
  5. 5.
    Edvinsson L., Ekblad E., Håkanson R., Wahlestedt C.: NPY potentiates the effect of various vasoconstrictor agents on rabbit blood vessels. Br. J. Pharmacol. 83: 519–525, 1984.PubMedCrossRefGoogle Scholar
  6. 6.
    Andriantsitohaina R., Stoclet J.C.: Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries. Br. J. Pharmacol. 95: 419–428, 1988.PubMedCrossRefGoogle Scholar
  7. 7.
    Vu H.Q., Budai D., Duckies S.P.: NPY preferentially potentiates responses to adrenergic nerve stimulation by increasing rate of contraction. J. Pharmacol. Exp. Ther. 251: 852–857, 1989.PubMedGoogle Scholar
  8. 8.
    Budai D., Vu H.Q., Duckies S.P.: Endothelium removal does not affect potentiation by neuropeptide Y in rabbit ear artery. Eur. J. Pharmacol 168: 97–100, 1989.PubMedCrossRefGoogle Scholar
  9. 9.
    Small D.L., Bolzon B.J., Cheung D.W.: Endothelium-independent potentiating effects of NPY in the rat tail artery. Eur. J. Pharmacol. 210: 131–136, 1992.PubMedCrossRefGoogle Scholar
  10. 10.
    Lundberg J.M., Pernow J., Tatemoto K., Dahlöf C.: Pre- and postjunctional effects of NPY on sympathetic control of rat femoral artery. Acta Physiol. Scand. 123:511–513, 1985.PubMedCrossRefGoogle Scholar
  11. 11.
    Chernaeva L., Charakchieva S.: Leucine-enkephalin and NPY-modulation of 3H-noradrenaline release in the oviduct of mature and juvenile rabbits. Gen. Pharmacol. 19: 137–142, 1988.PubMedCrossRefGoogle Scholar
  12. 12.
    Donoso V., Siva M., St.-Pierre S., Huidobro-Toro J.P.: NPY, an endogenous presynaptic modulator of adrenergic neurotransmission in rat vas deferens: structural and functional studies. Peptides 9: 545–553, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Grundemar L., Grundstrom N., Johansson I.G.M., Andersson R.G.G., Hakanson R.: Suppression by neuropeptide Y of capsaicin-sensitive sensory nerve-mediated contraction in guinea-pig airways. Br. J. Pharmacol. 99: 473–476, 1990.PubMedCrossRefGoogle Scholar
  14. 14.
    Kawasaki H., Nuki C., Saito A., Takasaki K.: NPY modulates neurotransmission of CGRP-containing vasodilator nerves in rat mesenteric arteries. Am. J. Physiol. 261: H683–H690, 1991.PubMedGoogle Scholar
  15. 15.
    Grundemar L., Hogestatt E.D.: Unmasking the vaso constrictor response to neuropeptide Y and its interaction with vasodilating agents in vitro. Eur. J. Pharmacol. 221: 71–76, 1992.PubMedCrossRefGoogle Scholar
  16. 16.
    Edvinsson L., Adamsson M.: NPY inhibits relaxation of guinea pig cerebral, coronary, and uterine arteries: blockade by d-myoinositol-1,2,6-trisphosphate. J. Cardiovasc. Pharmacol. 20: 466–472, 1992.PubMedCrossRefGoogle Scholar
  17. 17.
    Li Y., Duckies S.P.: Differential effects of NPY and opioids on neurogenic responses of the perfused rat mesentery. Eur. J. Pharmacol. 195: 365–372, 1991.PubMedCrossRefGoogle Scholar
  18. 18.
    Kenny R.A.: The respiratory and cardiovascular systems. In: Kenny R.A. (Ed.), Physiology of Aging. Year Book Medical Publishers, Chicago, 1989, pp. 49–65.Google Scholar
  19. 19.
    Timiras P.S.: Cardiovascular alterations with age: atherosclerosis, coronary heart disease, hypertension. In: Timiras P.S. (Ed.), Physiological Basis of Geriatrics. MacMillan Press, New York, 1988, pp. 268–289.Google Scholar
  20. 20.
    Chiueh C.C., Nespor S.M., Rapoport S.I.: Cardiovascular, sympathetic and adrenal cortical responsiveness of aged Fischer-344 rats to stress. Neurobiol. Aging 1: 157–163, 1980.CrossRefGoogle Scholar
  21. 21.
    Higuchi H., Yang H.Y.T., Costa E.: Age-related bidirectional changes in NPY peptides in rat adrenal glands, brain, and blood. J. Neurochem. 50: 1879–1886, 1988.PubMedCrossRefGoogle Scholar
  22. 22.
    Higuchi H., Yokokawa K., Iwasa A., Yoshida H., Miki N.: Age-dependent increase in NPY gene expression in rat adrenal gland and specific brain areas. J. Neurochem. 57: 1840–1847, 1991.PubMedCrossRefGoogle Scholar
  23. 23.
    Zoli M., Agnati F., Fuxe K., Zini I., Merlo Pich E., Grimaldi R., Härfstrand A., Goldstein M., Wikström A.C., Gustafsson J.Å.: Morphometrical and micro-densitometrical studies of PNMT and NPY immunore-active nerve terminals and on glucocorticoid receptor-immunoreactive nerve cell nuclei in the para ventricular nucleus in the adult and old male rats. Neuroscience 26: 479–492, 1988.PubMedCrossRefGoogle Scholar
  24. 24.
    Hetland M.L., Eldrup E., Bratholm P., Christensen N.J.: The relationship between age and venous plasma concentrations of noradrenaline, catecholamine metabolites, DOPA and NPY like immunoreactivity in normal human subjects. Scand. J. Clin. Lab. Invest. 51: 219–224, 1991.PubMedCrossRefGoogle Scholar
  25. 25.
    Miller D.W., Tessel R.E.: Age-dependent hyperresponsiveness of spontaneously hypertensive rats to the pressor effects of intravenous NPY: role of peptide administration and plasma NPY-like immunoreactivity. J. Cardiovasc. Pharmacol. 18: 647–656, 1991.PubMedCrossRefGoogle Scholar
  26. 26.
    Duckies S.P., Carter B.J., Williams C.L.: Vascular adrenergic neuroeffector function does not decline in rats. Circ. Res. 56: 109–116, 1985.CrossRefGoogle Scholar
  27. 27.
    Wahlestedt C., Edvinsson L., Ekblad E., Håkanson R.: NPY potentiates noradrenaline-evoked vasoconstriction: mode of action. J. Pharmacol. Exp. Ther. 234: 735–741, 1985.PubMedGoogle Scholar
  28. 28.
    Tschopl M., Miller R.C., Pelton J., Stoclet J.C., Bucher B.: Vasoconstrictor effects of neuropeptide Y analogues on the rat tail artery in the presence of phenylephrine. Br. J. Pharm. 110: 1098–1104, 1993.CrossRefGoogle Scholar
  29. 29.
    Glenn T.C., Edvinsson L., Duckies S.P.: Effects of NPY Y1 receptor are not antagonized by D-myo-inositol-1,2,6-trisphosphate. Soc. Neurosci. 19: A728, 1993.Google Scholar
  30. 30.
    Fallgren B., Arlock P., Edvinsson L.: Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction by an intracellular calcium-dependent mechanism. J. Auton. Nerv. Syst. 44: 155–159, 1993.CrossRefGoogle Scholar
  31. 31.
    Abel P., Han C.: Effects of neuropeptide Y on contraction, relaxation and membrane potential of rabbit cerebral arteries. J. Cardiovasc. Pharmacol. 13: 52–63, 1989.PubMedCrossRefGoogle Scholar
  32. 32.
    Edvinsson L., Adamsson M.: NPY inhibits relaxation of guinea pig cerebral, coronary, and uterine arteries: blockade by d-myoinositol-1,2,6-trisphosphate. J. Cardiovasc. Pharmacol. 20: 466–472, 1992.PubMedCrossRefGoogle Scholar
  33. 33.
    Fallgren B., Ekblad E., Edvinsson L.: Co-existence of neuropeptides and differential inhibition of vasodilator responses by NPY in guinea pig uterine arteries. Neurosci. Lett. 100: 71–76, 1989.PubMedCrossRefGoogle Scholar
  34. 34.
    Neild T.O.: Actions of NPY on innervated and denervated rat tail arteries. J. Physiol. 386: 19–30, 1987.PubMedGoogle Scholar
  35. 35.
    Li Z., Duckies S.P.: Acute effects of nicotine on rat mesenteric vasculature and tail artery. J. Pharmacol. Exp. Ther. 264: 1305–1309, 1993.PubMedGoogle Scholar
  36. 36.
    Buchholz J., Duckies S.P.: Effect of age on prejunctional modulation of norepinephrine release. J. Pharmacol. Exp. Ther. 252: 159–164, 1990.PubMedGoogle Scholar
  37. 37.
    Fuxe K., Agnati L.F., Kitayama I., Zoli M., Janson A.M., Härfstrand A., Vincent M., Kalia M., Goldstein M., Sassard J.: Evidence for discrete alterations in central cardiovascular catecholamine and NPY immunoreactive neurons in aged male rats. Eur. Heart J. 8: 139–145, 1987.PubMedCrossRefGoogle Scholar
  38. 38.
    Louis W.J., Conway E.L., Howes L.G., Maccarrone C., Beart P.M., Jarrott B.: Neurotransmitters and neuropeptides in blood pressure regulation in the spontaneously hypertensive rat. Can. J. Physiol. Pharmacol. 65: 1633–1637, 1987.PubMedCrossRefGoogle Scholar
  39. 39.
    Huguet F., Comoy E., Piriou A., Bohoun C.: Age-related changes of noradrenergic-NPY interaction in rat brain: norepinephrine, NPY levels and alpha-adrenoceptors. Brain Res. 625: 256–260, 1993.PubMedCrossRefGoogle Scholar
  40. 40.
    Beal M.F., Walker L.C., Storey E., Segar L., Price D.L., Cork L.C.: Neurotransmitters in neocortex of aged rhesus monkeys. Neurobiol. Aging 12: 407–412, 1993.CrossRefGoogle Scholar
  41. 41.
    Edvinsson L., Ekman R., Ottosson A.: Demonstration of perivascular peptides and changes in concentration with age in man. Gerontology 32: 50–52, 1986.PubMedCrossRefGoogle Scholar
  42. 42.
    Fouda A.K., Atkinson J.: Sensitivity to noradrenaline and electrical stimulation decreases with age in the rat tail artery. Naunyn-Schmiedeberg’s Arch. Pharmacol. 334: 37–39, 1986.CrossRefGoogle Scholar
  43. 43.
    Duckies S.P.: Reserpine-induced supersensitivity in rat caudal artery: influence of age. J. Pharmacol. Exp. Ther. 256: 513–518, 1990.Google Scholar
  44. 44.
    Stewart-Lee A.L., Aberdeen J., Burnstock G.: The effect of atherosclerosis on neuromodulation of sympathetic neurotransmission by NPY and CGRP in the rabbit mesenteric artery. Eur. J. Pharmacol 216: 167–174, 1992.PubMedCrossRefGoogle Scholar
  45. 45.
    Turek F.W., Desjardins C.: Development of Leydig cell tumors and onset of changes in the reproductive and endocrine systems of aging F344 rats. J. Natl. Cancer Inst. 63: 969–975, 1979.PubMedGoogle Scholar
  46. 46.
    Masoro E.J.: Use of rodents as models for the study of “normal aging”: Conceptual and practical issues. Neurobiol. Aging 12: 639–643, 1991.PubMedCrossRefGoogle Scholar
  47. 47.
    Gruenewald D.A., Hess D.L., Wilkinson C.W., Matsumoto A.M.: Excessive testicular progesterone secretion in aged male Fischer 344 rats: A potential cause of age-related gonadotropin suppression and confounding variable in aging studies. J. Gerontol. 47: B164–B170, 1992.PubMedCrossRefGoogle Scholar
  48. 48.
    Gruenewald D.A., Naai M.A., Hess D.L., Matsumoto AM.: The Brown Norway rat as a model of male reproductive aging: Evidence for both primary and secondary testicular failure. J. Gerontol 49: B42–B50, 1994.PubMedCrossRefGoogle Scholar
  49. 49.
    Hamil R.W., Schroeder B.: Hormonal regulation of adult sympathetic neurons: the effects of castration on neuropeptide Y, norepinephrine, and tyrosine hydroxylase activity. J. Neurobiol 21: 731–742, 1990.CrossRefGoogle Scholar
  50. 50.
    Li Z., Duckies S.P.: Influence of gender on vascular reactivity in the rat. J. Pharmacol Exp. Ther. 268: 1426–1431, 1991.Google Scholar
  51. 51.
    Eikenburg D.C.: Age-related changes in vascular sympathetic neurotransmission in the rat kidney. J. Pharmacol Exp. Ther. 259: 176–181, 1991.PubMedGoogle Scholar
  52. 52.
    Haass M., Cheng B., Richardt G., Lang R.E., Schömig A.: Characterization and presynaptic modulation of stimulation-evoked exocytotic co-release of noradrenaline and NPY in guinea pig heart. Naunyn-Schmiedeberg’s Arch. Pharmacol 339: 71–78, 1989.Google Scholar

Copyright information

© Springer Internal Publishing Switzerland 1994

Authors and Affiliations

  • Thomas C. Glenn
    • 1
  • S. P. Duckies
    • 1
  1. 1.Department of Pharmacology, College of MedicineUniversity of CaliforniaIrvineUSA

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