Vasoconstriction mediated by postsynaptic α2-adrenoceptor stimulation

  • P. B. M. W. M. Timmermans
  • P. A. van Zwieten


The postsynaptic α-adrenoceptors involved in vasoconstriction brought about by B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin) administered i.v. to pithed, normotensive rats were characterized. The rate of onset of the hypertensive response to i.v. B-HT 933 is slower than that induced by (−)-phenylephrine, an agonist of α1-adrenoceptor. The antagonism of the α-adrenoceptor blocking drugs rauwolscine, yohimbine and corynanthine was quantified towards B-HT 933-induced increases in diastolic pressure. Rauwolscine (pA2=7.06) and yohimbine (pA2=6.83) were effective antagonists, whereas corynanthine proved much less potent (pA2=5.03). On the basis of the reported selectivity of yohimbine and its two diastereoisomers rauwolscine and corynanthine for α1- and α2-adrenoceptor, it is concluded that the postsynaptic α-adrenoceptors triggered by B-HT 933 are of the α2-type. B-HT 933 identifies a subclass of postsynaptic α2-adrenoceptor in vascular smooth muscle distinct from postsynaptic α1-adrenoceptor. Both types of α-adrenoceptors are likely to be involved in the mediation of vasoconstriction.

Key words

B-HT 933 Yohimbine diastereoisomers Vasoconstriction Postsynaptic α2-adrenoceptor 


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  1. Arunlakshana, O., Schild, H. O.: Some quantitative uses of drug antagonists. Br. J. Pharmacol. Chemother. 14, 48–58 (1959)Google Scholar
  2. Berthelsen, S., Pettinger, W. A.: A functional basis for classification of α-adrenergic receptors. Life Sci. 21, 595–606 (1977)Google Scholar
  3. Borowski, E., Starke, K., Ehrl, H., Endo, T.: A comparison of pre- and postsynaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit. Neuroscience 2, 285–296 (1977)Google Scholar
  4. Docherty, J. R., McDonald, A., McGrath, J. C.: Further subclassification of α-adrenoceptors in the cardiovascular system, vas deferens and anococcygeus of the rat. Br. J. Pharmacol. 67, 421P-422P (1979)Google Scholar
  5. Drew, G. M.: Effects of α-adrenoceptor agonists and antagonists on pre- and postsynaptically located α-adrenoceptors. Eur. J. Pharmacol. 36, 313–320 (1976)Google Scholar
  6. Drew, G. M., Whiting, S. B.: Evidence for two distinct types of postsynaptic α-adrenoceptors in vascular smooth muscle in vivo. Br. J. Pharmacol. 67, 207–215 (1979)Google Scholar
  7. Kobinger, W., Pichler, L.: Pharmacological characterization of B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin·dihydrochloride) as a hypotensive agent of the “clonidine-type”. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 39–46 (1977)Google Scholar
  8. Starke, K., Borowski, E., Endo, T.: Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur. J. Pharmacol. 34, 385–388 (1975a)Google Scholar
  9. Starke, K., Endo, T., Taube, H. D.: Relative pre- and postsynaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn Schmiedeberg's Arch. Pharmacol. 291, 55–78 (1975b)Google Scholar
  10. Tanaka, T., Starke, K.: Binding of 3H-clonidine to an α-adrenoceptor in membranes of guinea-pig ileum. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 207–215 (1979)Google Scholar
  11. Timmermans, P. B. M. W. M.: A simple method for the discrimination between α1- and α2-adrenoceptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 311, R59 (1980)Google Scholar
  12. Timmermans, P. B. M. W. M.: Zwieten, P. A. van: Postsynaptic α1- and α2-adrenoceptor in the circulatory system of the pithed rat; selective stimulation of the 20-3 by B-HT 933. Eur. J. Pharmacol. 63, 199–202 (1980)Google Scholar
  13. Timmermans, P. B. M. W. M., Kwa, H. Y., Zwieten, P. A. van: Possible subdivision of postsynaptic α-adrenoceptors mediating pressor responses in the pithed rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 310, 189–193 (1979)Google Scholar
  14. Weitzell, R., Tanaka, T., Starke, K.: Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 127–136 (1979)Google Scholar
  15. Zwieten, P. A. van, Timmermans, P. B. M. W. M.: Centrally mediated hypotensive activity of B-HT 933 upon infusion via the cat's vertebral artery. Pharmacology (in press, 1980)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • P. B. M. W. M. Timmermans
    • 1
  • P. A. van Zwieten
    • 1
  1. 1.Department of Pharmacy, Division of PharmacotherapyUniversity of AmsterdamAmsterdamThe Netherlands

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