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Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction

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Abstract

We have studied the contractile effects of the sympathetic transmitter noradrenaline and its cotransmitter neuropeptide Y (NPY) given alone and in combination on isolated rat mesenteric resistance vessels (200–300 μm diameter). Noradrenaline and NPY each concentration-dependently contracted rat mesenteric microvessels (EC50 ≈ 800 nM and 10 nM, respectively), but noradrenaline caused considerably greater maximal effects than NPY (14.3 mN vs. 3.5mN). A low antagonistic potency of yohimbine indicated that the response to noradrenaline did not involve α2-adrenoceptors, and the subtype-selective antagonists 5-methylurapidil, tamsulosin and chloroethylclonidine indicated mediation via an α1A-adrenoceptor. Shallow Schild regressions for prazosin and 5-methylurapidil indicated that an α1-adrenoceptor subtype with relatively low prazosin affinity might additionally be involved. Studies with the NPY analogues PYY, [Leu31, Pro34]NPY and NPY18–36 demonstrated that NPY acted via a Y1 NPY receptor. In addition to its direct vasoconstricting effects NPY also lowered the noradrenaline EC50 but did not appreciably affect maximal noradrenaline responses indicating possible potentiation. The potentiating NPY response occured with similar agonist potency as the direct contractile NPY effects and also via a Y1 NPY receptor. The Ca2+ entry blocker nitrendipine (300 nM) reduced direct contractile responses to noradrenaline and NPY but did not affect the potentiation response to NPY.

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Authors and Affiliations

  1. Department of Medicine, University of Essen, Essen, Germany

    C. Fetscher, R.F. Schäfers, T. Philipp & M.C. Michel

  2. St. Elisabeth-Hospital, Herten, Germany

    H. Chen & G. Wambach

  3. Nephrologisches Labor IGI, Klinikum, Hufelandstrasse 55, D-45122, Essen, Germany

    M.C. Michel

Authors
  1. C. Fetscher
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  2. R.F. Schäfers
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  3. T. Philipp
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  4. M.C. Michel
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  5. H. Chen
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  6. G. Wambach
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Fetscher, C., Schäfers, R., Philipp, T. et al. Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction. Naunyn-Schmiedeberg's Arch Pharmacol 353, 314–323 (1996). https://doi.org/10.1007/BF00168634

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  • DOI: https://doi.org/10.1007/BF00168634

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