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. 1988 Oct;95(2):419–428. doi: 10.1111/j.1476-5381.1988.tb11662.x

Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries.

R Andriantsitohaina 1, J C Stoclet 1
PMCID: PMC1854192  PMID: 2465806

Abstract

1. The effects of neuropeptide Y (NPY) on resistance arteries were investigated on 3rd generation mesenteric arterioles of the rat. 2. Contractions were elicited by noradrenaline (NA), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha), depolarization (KCl substituted for NaCl) and by the calcium agonist Bay K 8644, in the absence and in the presence of NPY (100 nM), a concentration which by itself did not induce vasoconstriction. 3. NPY produced a leftward shift of the concentration-response curves to the agonists and to KCl, without any alteration of maximal contractions. 4. NPY also potentiated contractions elicited by addition of CaCl2 to KCl-depolarized vessels, but its effect on calcium-induced contractions decreased with increasing KCl concentrations (from 20 to 100 mM). 5. Calcium-induced contractions were inhibited by the calcium channel blocker nitrendipine, both in the presence and absence of NPY (100 nM). NPY increased slightly (but significantly) the sensitivity to nitrendipine (the apparent KB increased from 2.9 x 10(-10) M to 1.6 x 10(-10) M). 6. The KCl concentration necessary for the maximal effect of Bay K 8644 was decreased in the presence of NPY, and the sensitivity to the calcium channel agonist was increased. 7. Elevating the KCl concentration in the bath from 5 to 20 mM (which gives the same displacement to the left of the KCl concentration-effect curve seen in the presence of NPY) induced a parallel leftward shift of NA and 5-HT concentration-response curves. This shift was identical to the one induced by NPY on 5-HT-evoked contractions, but it was significantly smaller (P less than 0.001) than the shift of the NA concentration-response curve observed in the presence of NPY. In the latter case, NPY enhanced more markedly the contractions induced by low NA concentrations (between 10(-9) and 3 x 10(-8 M) than those induced by high concentrations (up to 3 x 10(-7) M), thus giving a shallow concentration-response curve. 8. The results strongly suggest that NPY partially depolarizes the arterioles and induces an increase in calcium entry through voltage-dependent channels, thus enhancing contractions elicited by agonists or by KCl-depolarization. In addition, they support the view that another mechanism also plays a part in the potentiation by NPY of the effects of low concentrations of NA.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dahlöf C., Dahlöf P., Lundberg J. M. Neuropeptide Y (NPY): enhancement of blood pressure increase upon alpha-adrenoceptor activation and direct pressor effects in pithed rats. Eur J Pharmacol. 1985 Feb 26;109(2):289–292. doi: 10.1016/0014-2999(85)90433-9. [DOI] [PubMed] [Google Scholar]
  3. Daly R. N., Hieble J. P. Neuropeptide Y modulates adrenergic neurotransmission by an endothelium dependent mechanism. Eur J Pharmacol. 1987 Jun 26;138(3):445–446. doi: 10.1016/0014-2999(87)90486-9. [DOI] [PubMed] [Google Scholar]
  4. Edvinsson L. Characterization of the contractile effect of neuropeptide Y in feline cerebral arteries. Acta Physiol Scand. 1985 Sep;125(1):33–41. doi: 10.1111/j.1748-1716.1985.tb07690.x. [DOI] [PubMed] [Google Scholar]
  5. Edvinsson L., Ekblad E., Håkanson R., Wahlestedt C. Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels. Br J Pharmacol. 1984 Oct;83(2):519–525. doi: 10.1111/j.1476-5381.1984.tb16516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edvinsson L., Emson P., McCulloch J., Tatemoto K., Uddman R. Neuropeptide Y: cerebrovascular innervation and vasomotor effects in the cat. Neurosci Lett. 1983 Dec 23;43(1):79–84. doi: 10.1016/0304-3940(83)90132-5. [DOI] [PubMed] [Google Scholar]
  7. Edvinsson L., Emson P., McCulloch J., Tatemoto K., Uddman R. Neuropeptide Y: immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ. Acta Physiol Scand. 1984 Oct;122(2):155–163. doi: 10.1111/j.1748-1716.1984.tb07493.x. [DOI] [PubMed] [Google Scholar]
  8. Ekblad E., Edvinsson L., Wahlestedt C., Uddman R., Håkanson R., Sundler F. Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept. 1984 Apr;8(3):225–235. doi: 10.1016/0167-0115(84)90064-8. [DOI] [PubMed] [Google Scholar]
  9. Evéquoz D., Waeber B., Corder R., Nussberger J., Gaillard R., Brunner H. R. Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y. Life Sci. 1987 Dec 7;41(23):2573–2580. doi: 10.1016/0024-3205(87)90442-5. [DOI] [PubMed] [Google Scholar]
  10. Fleming W. W. The electrogenic Na+, K+-pump in smooth muscle: physiologic and pharmacologic significance. Annu Rev Pharmacol Toxicol. 1980;20:129–149. doi: 10.1146/annurev.pa.20.040180.001021. [DOI] [PubMed] [Google Scholar]
  11. Fredholm B. B., Jansen I., Edvinsson L. Neuropeptide Y is a potent inhibitor of cyclic AMP accumulation in feline cerebral blood vessels. Acta Physiol Scand. 1985 Jul;124(3):467–469. doi: 10.1111/j.1748-1716.1985.tb07683.x. [DOI] [PubMed] [Google Scholar]
  12. Fuller R. W., Conradson T. B., Dixon C. M., Crossman D. C., Barnes P. J. Sensory neuropeptide effects in human skin. Br J Pharmacol. 1987 Dec;92(4):781–788. doi: 10.1111/j.1476-5381.1987.tb11381.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Furness J. B., Costa M., Emson P. C., Håkanson R., Moghimzadeh E., Sundler F., Taylor I. L., Chance R. E. Distribution, pathways and reactions to drug treatment of nerves with neuropeptide Y- and pancreatic polypeptide-like immunoreactivity in the guinea-pig digestive tract. Cell Tissue Res. 1983;234(1):71–92. doi: 10.1007/BF00217403. [DOI] [PubMed] [Google Scholar]
  14. Furness J. B., Costa M., Keast J. R. Choline acetyltransferase- and peptide immunoreactivity of submucous neurons in the small intestine of the guinea-pig. Cell Tissue Res. 1984;237(2):329–336. doi: 10.1007/BF00217152. [DOI] [PubMed] [Google Scholar]
  15. Glover W. E. Increased sensitivity of rabbit ear artery to noradrenaline following perivascular nerve stimulation may be a response to neuropeptide Y released as cotransmitter. Clin Exp Pharmacol Physiol. 1985 May-Jun;12(3):227–230. doi: 10.1111/j.1440-1681.1985.tb02636.x. [DOI] [PubMed] [Google Scholar]
  16. Gray T. S., Morley J. E. Neuropeptide Y: anatomical distribution and possible function in mammalian nervous system. Life Sci. 1986 Feb 3;38(5):389–401. doi: 10.1016/0024-3205(86)90061-5. [DOI] [PubMed] [Google Scholar]
  17. Hanko J. H., Törnebrandt K., Hardebo J. E., Kåhrström J., Nobin A., Owman C. Neuropeptide Y induces and modulates vasoconstriction in intracranial and peripheral vessels of animals and man. J Auton Pharmacol. 1986 Jun;6(2):117–124. doi: 10.1111/j.1474-8673.1986.tb00638.x. [DOI] [PubMed] [Google Scholar]
  18. Hassall C. J., Burnstock G. Immunocytochemical localisation of neuropeptide Y and 5-hydroxytryptamine in a subpopulation of amine-handling intracardiac neurones that do not contain dopamine beta-hydroxylase in tissue culture. Brain Res. 1987 Sep 29;422(1):74–82. doi: 10.1016/0006-8993(87)90541-5. [DOI] [PubMed] [Google Scholar]
  19. Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
  20. Häggblad J., Fredholm B. B. Adenosine and neuropeptide Y enhance alpha 1-adrenoceptor-induced accumulation of inositol phosphates and attenuate forskolin-induced accumulation of cyclic AMP in rat vas deferens. Neurosci Lett. 1987 Nov 23;82(2):211–216. doi: 10.1016/0304-3940(87)90132-7. [DOI] [PubMed] [Google Scholar]
  21. Julou G., Freslon J. L. Effects of calcium entry blockers on Ca2+-induced contraction of depolarized and noradrenaline-exposed rat resistance vessels. Eur J Pharmacol. 1986 Oct 7;129(3):261–270. doi: 10.1016/0014-2999(86)90436-x. [DOI] [PubMed] [Google Scholar]
  22. Kassis S., Olasmaa M., Terenius L., Fishman P. H. Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. J Biol Chem. 1987 Mar 15;262(8):3429–3431. [PubMed] [Google Scholar]
  23. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  24. Lundberg J. M., Hemsén A., Larsson O., Rudehill A., Saria A., Fredholm B. B. Neuropeptide Y receptor in pig spleen: binding characteristics, reduction of cyclic AMP formation and calcium antagonist inhibition of vasoconstriction. Eur J Pharmacol. 1988 Jan 5;145(1):21–29. doi: 10.1016/0014-2999(88)90344-5. [DOI] [PubMed] [Google Scholar]
  25. Lundberg J. M., Pernow J., Franco-Cereceda A., Rudehill A. Effects of antihypertensive drugs on sympathetic vascular control in relation to neuropeptide Y. J Cardiovasc Pharmacol. 1987;10 (Suppl 12):S51–S68. [PubMed] [Google Scholar]
  26. Lundberg J. M., Tatemoto K. Pancreatic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to alpha-adrenoceptor blockade. Acta Physiol Scand. 1982 Dec;116(4):393–402. doi: 10.1111/j.1748-1716.1982.tb07157.x. [DOI] [PubMed] [Google Scholar]
  27. Lundberg J. M., Terenius L., Hökfelt T., Martling C. R., Tatemoto K., Mutt V., Polak J., Bloom S., Goldstein M. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand. 1982 Dec;116(4):477–480. doi: 10.1111/j.1748-1716.1982.tb07171.x. [DOI] [PubMed] [Google Scholar]
  28. Mabe Y., Pérez R., Tatemoto K., Huidobro-Toro J. P. Chemical sympathectomy reveals pre- and postsynaptic effects of neuropeptide Y (NPY) in the cardiovascular system. Experientia. 1987 Sep 15;43(9):1018–1020. doi: 10.1007/BF01952225. [DOI] [PubMed] [Google Scholar]
  29. Mabe Y., Tatemoto K., Huidobro-Toro J. P. Neuropeptide Y-induced pressor responses: activation of a non-adrenergic mechanism, potentiation by reserpine and blockade by nifedipine. Eur J Pharmacol. 1985 Oct 8;116(1-2):33–39. doi: 10.1016/0014-2999(85)90182-7. [DOI] [PubMed] [Google Scholar]
  30. Mulvany M. J., Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977 Jul;41(1):19–26. doi: 10.1161/01.res.41.1.19. [DOI] [PubMed] [Google Scholar]
  31. Mulvany M. J., Nilsson H., Flatman J. A. Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation. J Physiol. 1982 Nov;332:363–373. doi: 10.1113/jphysiol.1982.sp014418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mulvany M. J. The fourth Sir George Pickering memorial lecture. The structure of the resistance vasculature in essential hypertension. J Hypertens. 1987 Apr;5(2):129–136. doi: 10.1097/00004872-198704000-00001. [DOI] [PubMed] [Google Scholar]
  33. Neild T. O. Actions of neuropeptide Y on innervated and denervated rat tail arteries. J Physiol. 1987 May;386:19–30. doi: 10.1113/jphysiol.1987.sp016519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nilsson H. Adrenergic nervous control of resistance and capacitance vessels. Studies on isolated blood vessels from the rat. Acta Physiol Scand Suppl. 1985;541:1–34. [PubMed] [Google Scholar]
  35. O'Donohue T. L., Chronwall B. M., Pruss R. M., Mezey E., Kiss J. Z., Eiden L. E., Massari V. J., Tessel R. E., Pickel V. M., DiMaggio D. A. Neuropeptide Y and peptide YY neuronal and endocrine systems. Peptides. 1985 Jul-Aug;6(4):755–768. doi: 10.1016/0196-9781(85)90180-9. [DOI] [PubMed] [Google Scholar]
  36. Pernow J., Svenberg T., Lundberg J. M. Actions of calcium antagonists on pre- and postjunctional effects of neuropeptide Y on human peripheral blood vessels in vitro. Eur J Pharmacol. 1987 Apr 14;136(2):207–218. doi: 10.1016/0014-2999(87)90712-6. [DOI] [PubMed] [Google Scholar]
  37. Petrenko S., Olianas M. C., Onali P., Gessa G. L. Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase activity in rat hippocampus. Eur J Pharmacol. 1987 Apr 29;136(3):425–428. doi: 10.1016/0014-2999(87)90318-9. [DOI] [PubMed] [Google Scholar]
  38. Sanguinetti M. C., Kass R. S. Voltage-dependent block of calcium channel current in the calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res. 1984 Sep;55(3):336–348. doi: 10.1161/01.res.55.3.336. [DOI] [PubMed] [Google Scholar]
  39. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]
  40. Serfozo P., Bartfai T., Vizi E. S. Presynaptic effects of neuropeptide Y on [3H]noradrenaline and [3H]acetylcholine release. Regul Pept. 1986 Dec 22;16(2):117–123. doi: 10.1016/0167-0115(86)90055-8. [DOI] [PubMed] [Google Scholar]
  41. Tatemoto K., Carlquist M., Mutt V. Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982 Apr 15;296(5858):659–660. doi: 10.1038/296659a0. [DOI] [PubMed] [Google Scholar]
  42. Wahlestedt C., Edvinsson L., Ekblad E., Håkanson R. Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action. J Pharmacol Exp Ther. 1985 Sep;234(3):735–741. [PubMed] [Google Scholar]
  43. Wahlestedt C., Yanaihara N., Håkanson R. Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept. 1986 Feb;13(3-4):307–318. doi: 10.1016/0167-0115(86)90048-0. [DOI] [PubMed] [Google Scholar]
  44. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  45. Zukowska-Grojec Z., Haass M., Bayorh M. A. Neuropeptide Y and peptide YY mediate nonadrenergic vasoconstriction and modulate sympathetic responses in rats. Regul Pept. 1986 Sep;15(2):99–110. doi: 10.1016/0167-0115(86)90080-7. [DOI] [PubMed] [Google Scholar]

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