Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Mar;105(3):542–548. doi: 10.1111/j.1476-5381.1992.tb09016.x

Influence of anaesthesia on the cardiovascular effects of rilmenidine and clonidine in spontaneously hypertensive rats.

F Sannajust 1, C Cerutti 1, E Koenig-Bérard 1, J Sassard 1
PMCID: PMC1908436  PMID: 1352719

Abstract

1. The acute cardiovascular effects of two alpha 2-adrenoceptor agonists, rilmenidine and clonidine, were studied in 15-week-old male spontaneously hypertensive rats (SHRs). The effects of these drugs were compared with intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in conscious and pentobarbitone-anaesthetized SHRs, in which aortic blood pressure (BP) was continuously recorded. 2. In conscious SHRs, i.v. doses of either rilmenidine (30, 100, 300 micrograms kg-1) or clonidine (3, 10, 30 micrograms kg-1) induced dose-dependent short-lasting increases in BP followed by moderate decreases associated with bradycardia, while the same three doses of both drugs given i.c.v. were devoid of BP and heart rate (HR) effects. 3. Pentobarbitone-anaesthesia increased the sympathetic control of BP and suppressed the cardiac baroreflex sensitivity. 4. In anaesthetized SHRs, i.v. injections of the same 3 doses of rilmenidine and clonidine induced a slight increase in BP, rapidly followed by profound and long-lasting BP and HR decreases. Surprisingly, when given i.c.v., these 3 doses lowered BP and HR to the same extent but in a more progressive manner. 5. The lack of efficacy of both drugs in conscious SHRs after the i.c.v. administration of i.v. active doses and the lack of more marked and rapid effects in anaesthetized SHRs, after i.c.v. than after i.v. injections, question the involvement of a major central site of action for these antihypertensive alpha 2-adrenoceptor agonists. Moreover, these results show that the cardiovascular effects of these drugs are profoundly influenced by baseline sympathetic nervous system activity which is enhanced by pentobarbitone-anaesthesia.

Full text

PDF
542

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baum T., Becker F. T. Hypotensive and postural effects of the gamma-aminobutyric acid agonist muscimol and of clonidine. J Cardiovasc Pharmacol. 1982 Mar-Apr;4(2):165–169. doi: 10.1097/00005344-198203000-00001. [DOI] [PubMed] [Google Scholar]
  2. Bonham A. C., Trapani A. J., Portis L. R., Brody M. J. Studies on the mechanism of the central antihypertensive effect of guanabenz and clonidine. J Hypertens Suppl. 1984 Dec;2(3):S543–S546. [PubMed] [Google Scholar]
  3. Bousquet P., Feldman J. The blood pressure effects of alpha-adrenoceptor antagonists injected in the medullary site of action of clonidine: the nucleus reticularis lateralis. Life Sci. 1987 Mar 16;40(11):1045–1052. doi: 10.1016/0024-3205(87)90566-2. [DOI] [PubMed] [Google Scholar]
  4. Cerutti C., Barres C., Paultre C. Z., Sassard J. Computer analysis of intraarterially recorded blood pressure in conscious unrestrained rats. J Pharmacol Methods. 1985 Jun;13(3):249–260. doi: 10.1016/0160-5402(85)90025-7. [DOI] [PubMed] [Google Scholar]
  5. Connor H. E., Finch L. Postsynaptic spinal alpha-adrenoceptors mediate effects of intrathecal clonidine. Eur J Pharmacol. 1981 Nov 19;76(1):97–100. doi: 10.1016/0014-2999(81)90015-7. [DOI] [PubMed] [Google Scholar]
  6. Ernsberger P., Giuliano R., Willette R. N., Reis D. J. Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla. J Pharmacol Exp Ther. 1990 Apr;253(1):408–418. [PubMed] [Google Scholar]
  7. Fillastre J. P., Letac B., Galinier F., Le Bihan G., Schwartz J. A multicenter double-blind comparative study of rilmenidine and clonidine in 333 hypertensive patients. Am J Cardiol. 1988 Feb 24;61(7):81D–85D. doi: 10.1016/0002-9149(88)90471-7. [DOI] [PubMed] [Google Scholar]
  8. Galley P., Manciet G., Hessel J. L., Michel J. P. Antihypertensive efficacy and acceptability of rilmenidine in elderly hypertensive patients. Am J Cardiol. 1988 Feb 24;61(7):86D–90D. doi: 10.1016/0002-9149(88)90472-9. [DOI] [PubMed] [Google Scholar]
  9. Gomez R. E., Ernsberger P., Feinland G., Reis D. J. Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area. Eur J Pharmacol. 1991 Mar 26;195(2):181–191. doi: 10.1016/0014-2999(91)90534-w. [DOI] [PubMed] [Google Scholar]
  10. Guicheney P., Dausse J. P., Meyer P. Affinités respectives du S3341 et de la clonidine pour les recepteurs adrénergiques alpha1 et alpha 2 du cerveau du rat. J Pharmacol. 1981 Jul-Sep;12(3):255–262. [PubMed] [Google Scholar]
  11. Gustin M. P., Cerutti C., Paultre C. Z. Heterogeneous computer network for real-time hemodynamic signal processing. Comput Biol Med. 1990;20(3):205–215. doi: 10.1016/0010-4825(90)90006-b. [DOI] [PubMed] [Google Scholar]
  12. Hoffman W. E., Phillips M. I., Schmid P. G. Central angiotensin II-induced responses in spontaneously hypertensive rats. Am J Physiol. 1977 Apr;232(4):H426–H433. doi: 10.1152/ajpheart.1977.232.4.H426. [DOI] [PubMed] [Google Scholar]
  13. Jarrott B., Conway E. L., Maccarrone C., Lewis S. J. Clonidine: understanding its disposition, sites and mechanism of action. Clin Exp Pharmacol Physiol. 1987 May;14(5):471–479. doi: 10.1111/j.1440-1681.1987.tb00999.x. [DOI] [PubMed] [Google Scholar]
  14. Kawasaki H., Takasaki K. Central alpha-2 adrenoceptor-mediated hypertensive response to clonidine in conscious, normotensive rats. J Pharmacol Exp Ther. 1986 Mar;236(3):810–818. [PubMed] [Google Scholar]
  15. Kawasaki H., Yamamoto R., Takasaki K. Possible mechanisms underlying the hypertensive response to clonidine in freely moving, normotensive rats. Jpn J Pharmacol. 1986 Nov;42(3):405–417. doi: 10.1254/jjp.42.405. [DOI] [PubMed] [Google Scholar]
  16. Kobinger W., Pichler L. Localization in the CNA of adrenoceptors which facilitate a cardioinhibitory reflex. Naunyn Schmiedebergs Arch Pharmacol. 1975;286(4):371–377. doi: 10.1007/BF00506651. [DOI] [PubMed] [Google Scholar]
  17. Lachaud V., Coupry I., Podevin R. A., Dausse J. P., Koenig E., Parini A. Interaction of clonidine and rilmenidine with imidazoline-preferring receptors. J Hypertens Suppl. 1988 Dec;6(4):S511–S513. doi: 10.1097/00004872-198812040-00161. [DOI] [PubMed] [Google Scholar]
  18. Laubie M., Poignant J. C., Scuvée-Moreau J., Dabire H., Dresse A., Schmitt H. Pharmacological properties of (N-dicyclopropylmethyl) amino-2-oxazoline (S 3341), an alpha-2 adrenoceptor agonist. J Pharmacol. 1985 Jul-Sep;16(3):259–278. [PubMed] [Google Scholar]
  19. Matsukawa K., Ninomiya I. Anesthetic effects on tonic and reflex renal sympathetic nerve activity in awake cats. Am J Physiol. 1989 Feb;256(2 Pt 2):R371–R378. doi: 10.1152/ajpregu.1989.256.2.R371. [DOI] [PubMed] [Google Scholar]
  20. Meeley M. P., Ernsberger P. R., Granata A. R., Reis D. J. An endogenous clonidine-displacing substance from bovine brain: receptor binding and hypotensive actions in the ventrolateral medulla. Life Sci. 1986 Mar 24;38(12):1119–1126. doi: 10.1016/0024-3205(86)90248-1. [DOI] [PubMed] [Google Scholar]
  21. Palaić D., Page I. H., Khairallah P. A. Uptake and metabolism of [14C] serotonin in rat brain. J Neurochem. 1967 Jan;14(1):63–69. doi: 10.1111/j.1471-4159.1967.tb09494.x. [DOI] [PubMed] [Google Scholar]
  22. Punnen S., Urbanski R., Krieger A. J., Sapru H. N. Ventrolateral medullary pressor area: site of hypotensive action of clonidine. Brain Res. 1987 Oct 6;422(2):336–346. doi: 10.1016/0006-8993(87)90941-3. [DOI] [PubMed] [Google Scholar]
  23. Sannajust F., Julien C., Barrès C., Cerutti C., Koenig-Bérard E., Sassard J. Cardiovascular effects of rilmenidine, a new alpha 2-adrenoceptor agonist, and clonidine in conscious spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 1989 Nov;16(11):837–848. doi: 10.1111/j.1440-1681.1989.tb01523.x. [DOI] [PubMed] [Google Scholar]
  24. Smyth H. S., Sleight P., Pickering G. W. Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. Circ Res. 1969 Jan;24(1):109–121. doi: 10.1161/01.res.24.1.109. [DOI] [PubMed] [Google Scholar]
  25. Solomon R. E., Brody M. J., Gebhart G. F. Pharmacological characterization of alpha adrenoceptors involved in the antinociceptive and cardiovascular effects of intrathecally administered clonidine. J Pharmacol Exp Ther. 1989 Oct;251(1):27–38. [PubMed] [Google Scholar]
  26. Sun M. K., Guyenet P. G. Effect of clonidine and gamma-aminobutyric acid on the discharges of medullo-spinal sympathoexcitatory neurons in the rat. Brain Res. 1986 Mar 12;368(1):1–17. doi: 10.1016/0006-8993(86)91036-x. [DOI] [PubMed] [Google Scholar]
  27. Tibirica E., Feldman J., Bousquet P. Differences in the ability of yohimbine to antagonize the hypotensive effect of clonidine in normotensive and spontaneously hypertensive anesthetized rats. J Pharmacol Exp Ther. 1988 Mar;244(3):1062–1066. [PubMed] [Google Scholar]
  28. Timmermans P. B., Van Zwieten P. A. Postsynaptic alpha 1- and alpha 2-adrenoceptors in the circulatory system of the pithed rat: selective stimulation of the alpha 2-type by B-HT 933. Eur J Pharmacol. 1980 May 2;63(2-3):199–202. doi: 10.1016/0014-2999(80)90446-x. [DOI] [PubMed] [Google Scholar]
  29. Touw K. B., Haywood J. R., Shaffer R. A., Brody M. J. Contribution of the sympathetic nervous system to vascular resistance in conscious young and adult spontaneously hypertensive rats. Hypertension. 1980 Jul-Aug;2(4):408–418. doi: 10.1161/01.hyp.2.4.408. [DOI] [PubMed] [Google Scholar]
  30. Van Zwieten P. A. Pharmacology of the alpha 2-adrenoceptor agonist rilmenidine. Am J Cardiol. 1988 Feb 24;61(7):6D–14D. doi: 10.1016/0002-9149(88)90457-2. [DOI] [PubMed] [Google Scholar]
  31. van Zwieten P. A., Thoolen M. J., Jonkman F. A., Wilffert B., de Jonge A., Timmermans P. B. Central and peripheral effects of S 3341 [(N-dicyclopropylmethyl)-amino-2-oxazoline] in animal models. Arch Int Pharmacodyn Ther. 1986 Jan;279(1):130–149. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES