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. 1990 Oct;101(2):329–336. doi: 10.1111/j.1476-5381.1990.tb12710.x

Reserpine induces vascular alpha 2-adrenergic supersensitivity and platelet alpha 2-adrenoceptor up-regulation in dog.

L Estan 1, J M Senard 1, M A Tran 1, J L Montastruc 1, M Berlan 1
PMCID: PMC1917705  PMID: 2175232

Abstract

1. The aim of the present study was to investigate the influence of catecholamine levels on the regulation of alpha 2-adrenoceptor sensitivity in dogs. 2. Blood pressure and heart rate values at rest, plasma catecholamine levels, platelet and adipocyte alpha 2-adrenoceptors as well as the alpha 2-mediated cardiovascular responses to clonidine (10 micrograms kg-1 i.v., after alpha 1-, beta-adrenoceptor plus muscarinic blockade) or noradrenaline (0.5, 1, 2 and 4 micrograms kg-1 i.v. after alpha 1- and beta-adrenoceptor blockade) were measured before and after reserpine treatment (0.1 mg kg-1 day-1 s.c. over 15 days). 3. Reserpine induced a significant decrease in resting systolic and diastolic blood pressures (213 +/- 2/87 +/- 6 mmHg before vs 158 +/- 5/59 +/- 3 mmHg after treatment) as well as in heart rate (91 +/- 2 beats min-1 before vs 76 +/- 3 beats min-1 after treatment). 4. A 5 min tilt test performed under chloralose anesthesia, failed to modify blood pressure before treatment whereas it induced a significant fall in the same animals after the 15 day treatment. Plasma levels of noradrenaline significantly decreased (262 +/- 58 vs 66 +/- 31 pg ml-1) whereas plasma adrenaline levels were unchanged. 5. The alpha 2-mediated pressor responses to noradrenaline were significantly increased after reserpine. Clonidine induced a marked pressor effect (+72 and +45% in systolic and diastolic blood pressures respectively) after reserpine treatment. This effect was suppressed by administration of RX-821002, a new specific alpha 2-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Berlan M., Lafontan M. Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha 2 adrenoceptor properties. Eur J Clin Invest. 1985 Dec;15(6):341–348. doi: 10.1111/j.1365-2362.1985.tb00282.x. [DOI] [PubMed] [Google Scholar]
  2. Berlan M., Lafontan M. Identification of alpha 2-adrenergic receptors in human fat cell membranes by [3H]chlonidine binding. Eur J Pharmacol. 1980 Oct 31;67(4):481–484. doi: 10.1016/0014-2999(80)90191-0. [DOI] [PubMed] [Google Scholar]
  3. Bobik A., Anderson W. P. Influence of sympathectomy on alpha 2 adrenoceptor binding sites in canine blood vessels. Life Sci. 1983 Jul 25;33(4):331–336. doi: 10.1016/s0024-3205(83)80005-8. [DOI] [PubMed] [Google Scholar]
  4. Broadley K. J., Lumley P. Selective reserpine-induced supersensitivity of the positive inotropic and chronotropic responses to isoprenaline and salbutamol in guinea-pig isolated atria. Br J Pharmacol. 1977 Jan;59(1):51–60. doi: 10.1111/j.1476-5381.1977.tb06976.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brodde O. E. Endogenous and exogenous regulation of human alpha- and beta-adrenergic receptors. J Recept Res. 1983;3(1-2):151–162. doi: 10.3109/10799898309041930. [DOI] [PubMed] [Google Scholar]
  6. Bylund D. B., Martinez J. R. alpha 2-Adrenergic receptors appear in rat salivary glands after reserpine treatment. Nature. 1980 May 22;285(5762):229–230. doi: 10.1038/285229a0. [DOI] [PubMed] [Google Scholar]
  7. Carpene C., Berlan M., Lafontan M. Influence of development and reduction of fat stores on the antilipolytic alpha 2-adrenoceptor in hamster adipocytes: comparison with adenosine and beta-adrenergic lipolytic responses. J Lipid Res. 1983 Jun;24(6):766–774. [PubMed] [Google Scholar]
  8. Chess-Williams R. G., Grassby P. F., Broadley K. J., Sheridan D. J. Cardiac alpha- and beta-adrenoceptor sensitivity and binding characteristics after chronic reserpine pretreatment. Naunyn Schmiedebergs Arch Pharmacol. 1987 Dec;336(6):646–651. doi: 10.1007/BF00165755. [DOI] [PubMed] [Google Scholar]
  9. Crampes F., Marceron M., Beauville M., Riviere D., Garrigues M., Berlan M., Lafontan M. Platelet alpha 2-adrenoceptors and adrenergic adipose tissue responsiveness after moderate hypocaloric diet in obese subjects. Int J Obes. 1989;13(1):99–110. [PubMed] [Google Scholar]
  10. Daly R. N., Sulpizio A. C., Levitt B., DeMarinis R. M., Regan J. W., Ruffolo R. R., Jr, Hieble J. P. Evidence for heterogeneity between pre- and postjunctional alpha-2 adrenoceptors using 9-substituted 3-benzazepines. J Pharmacol Exp Ther. 1988 Oct;247(1):122–128. [PubMed] [Google Scholar]
  11. Deighton N. M., Brown A. D., Hamilton C. A., Reid J. L. Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit. Naunyn Schmiedebergs Arch Pharmacol. 1988 Nov;338(5):517–522. doi: 10.1007/BF00179323. [DOI] [PubMed] [Google Scholar]
  12. Deighton N. M., Hamilton C. A., Jones C. R., Reid J. L. The effects of chronic administration of adrenaline on the function and number of adrenoceptors in the rabbit. J Cardiovasc Pharmacol. 1988 Sep;12(3):332–337. doi: 10.1097/00005344-198809000-00011. [DOI] [PubMed] [Google Scholar]
  13. FLEMING W. W., TRENDELENBURG U. The development of supersensitivity to norepinephrine after pretreatment with reserpine. J Pharmacol Exp Ther. 1961 Jul;133:41–51. [PubMed] [Google Scholar]
  14. Fleming W. W., McPhillips J. J., Westfall D. P. Postjunctional supersensitivity and subsensitivity of excitable tissues to drugs. Ergeb Physiol. 1973;68:55–119. doi: 10.1007/3-540-06238-6_5. [DOI] [PubMed] [Google Scholar]
  15. Fortin T. L., Sundaresan P. R. Reserpine but not surgical denervation regulates rat renal beta-adrenergic receptors. Am J Physiol. 1989 Apr;256(4 Pt 2):F532–F539. doi: 10.1152/ajprenal.1989.256.4.F532. [DOI] [PubMed] [Google Scholar]
  16. Hawthorn M. H., Broadley K. J. Reserpine-induced supersensitivity occurs for beta-adrenoceptor-mediated responses of heart and trachea but not of the uterus and lung. Eur J Pharmacol. 1984 Oct 15;105(3-4):245–255. doi: 10.1016/0014-2999(84)90616-2. [DOI] [PubMed] [Google Scholar]
  17. Häggendal J., Dahlström A. The recovery of noradrenaline in adrenergic nerve terminals of the rat after reserpine treatment. J Pharm Pharmacol. 1971 Feb;23(2):81–89. doi: 10.1111/j.2042-7158.1971.tb08617.x. [DOI] [PubMed] [Google Scholar]
  18. Lafontan M., Berlan M. Characterization of physiological agonist selectivity of human fat cell alpha 2-adrenoceptors: adrenaline is the major stimulant of the alpha 2-adrenoceptors. Eur J Pharmacol. 1982 Aug 13;82(1-2):107–111. doi: 10.1016/0014-2999(82)90562-3. [DOI] [PubMed] [Google Scholar]
  19. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  20. Langin D., Lafontan M., Stillings M. R., Paris H. [3H]RX821002: a new tool for the identification of alpha 2A-adrenoceptors. Eur J Pharmacol. 1989 Aug 11;167(1):95–104. doi: 10.1016/0014-2999(89)90751-6. [DOI] [PubMed] [Google Scholar]
  21. Latifpour J., McNeill J. H. Reserpine-induced changes in cardiac adrenergic receptors. Can J Physiol Pharmacol. 1984 Jan;62(1):23–26. doi: 10.1139/y84-003. [DOI] [PubMed] [Google Scholar]
  22. Linde B., Hjemdahl P. Effect of tilting on adipose tissue vascular resistance and sympathetic activity in humans. Am J Physiol. 1982 Feb;242(2):H161–H167. doi: 10.1152/ajpheart.1982.242.2.H161. [DOI] [PubMed] [Google Scholar]
  23. Mahan L. C., McKernan R. M., Insel P. A. Metabolism of alpha- and beta-adrenergic receptors in vitro and in vivo. Annu Rev Pharmacol Toxicol. 1987;27:215–235. doi: 10.1146/annurev.pa.27.040187.001243. [DOI] [PubMed] [Google Scholar]
  24. Marcus C., Karpe B., Bolme P., Sonnenfeld T., Arner P. Changes in catecholamine-induced lipolysis in isolated human fat cells during the first year of life. J Clin Invest. 1987 Jun;79(6):1812–1818. doi: 10.1172/JCI113022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nasseri A., Barakeh J. F., Abel P. W., Minneman K. P. Reserpine-induced postjunctional supersensitivity in rat vas deferens and caudal artery without changes in alpha adrenergic receptors. J Pharmacol Exp Ther. 1985 Aug;234(2):350–357. [PubMed] [Google Scholar]
  26. Roscher A. A., Wiesmann U. N., Honegger U. E. Changes in beta adrenergic receptors in submaxillary glands of chronically reserpine- or isoproterenol-treated rats. J Pharmacol Exp Ther. 1981 Feb;216(2):419–424. [PubMed] [Google Scholar]
  27. Saulnier-Blache J. S., Carpéné C., Langin D., Lafontan M. Imidazolinic radioligands for the identification of hamster adipocyte alpha 2-adrenoceptors. Eur J Pharmacol. 1989 Nov 21;171(2-3):145–157. doi: 10.1016/0014-2999(89)90103-9. [DOI] [PubMed] [Google Scholar]
  28. Stiles G. L., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev. 1984 Apr;64(2):661–743. doi: 10.1152/physrev.1984.64.2.661. [DOI] [PubMed] [Google Scholar]
  29. Taouis M., Berlan M., Lafontan M. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine. Mol Pharmacol. 1987 Jan;31(1):89–96. [PubMed] [Google Scholar]
  30. Taouis M., Berlan M., Montastruc P., Lafontan M. Characterization of dog fat cell adrenoceptors: variations in alpha-2 and beta adrenergic receptors distribution according to the extent of the fat deposits and the anatomical location. J Pharmacol Exp Ther. 1987 Sep;242(3):1041–1049. [PubMed] [Google Scholar]
  31. Tenner T. E., Jr, Mukherjee A., Hester R. K. Reserpine-induced supersensitivity and the proliferation of cardiac beta-adrenoceptors. Eur J Pharmacol. 1982 Jan 8;77(1):61–65. doi: 10.1016/0014-2999(82)90537-4. [DOI] [PubMed] [Google Scholar]
  32. Timmermans P. B., van Zwieten P. A. Mini-review. The postsynaptic alpha 2-adrenoreceptor. J Auton Pharmacol. 1981 Mar;1(2):171–183. doi: 10.1111/j.1474-8673.1981.tb00509.x. [DOI] [PubMed] [Google Scholar]
  33. Valet P., Tran M. A., Damase-Michel C., de Saint-Blanquat G., Dang Tran L., Anglade F., Koenig-Berard E., Montastruc J. L. Rilmenidine (S 3341) and the sympathoadrenal system: adrenoreceptors, plasma and adrenal catecholamines in dogs. J Auton Pharmacol. 1988 Dec;8(4):319–326. doi: 10.1111/j.1474-8673.1988.tb00575.x. [DOI] [PubMed] [Google Scholar]
  34. Villeneuve A., Berlan M., Lafontan M., Montastruc J. L. Characterization of dog platelet alpha-adrenergic receptor: lack of in vivo down regulation by adrenergic agonist treatments. Comp Biochem Physiol C. 1985;81(1):181–187. doi: 10.1016/0742-8413(85)90112-4. [DOI] [PubMed] [Google Scholar]
  35. Watanabe Y., Lai R. T., Maeda H., Yoshida H. Reserpine and sympathetic denervation cause an increase of postsynaptic alpha 2-adrenoceptors. Eur J Pharmacol. 1982 May 7;80(1):105–108. doi: 10.1016/0014-2999(82)90183-2. [DOI] [PubMed] [Google Scholar]

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