Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 May;77(5):1416–1421. doi: 10.1172/JCI112452

Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets.

A S Hollister, J Onrot, S Lonce, J H Nadeau, D Robertson
PMCID: PMC424540  PMID: 3009543

Abstract

We measured alpha 2-adrenoreceptor density as well as affinity for and sensitivity to agonist on intact platelets of normotensive and hypertensive subjects before and after physiological increases in plasma catecholamines. In normotensives, posture-induced rises in plasma catecholamines correlated with reduced alpha 2-adrenoreceptor agonist affinity and fewer high affinity state receptors. Platelet aggregation and inhibition of adenylate cyclase by L-epinephrine also was reduced. Hypertensive subjects had similar rises in plasma catecholamines with upright posture, but showed no change in receptor affinity or sensitivity. No change in platelet alpha 2-adrenoreceptor number occurred in these studies. In vitro incubation with L-epinephrine revealed that platelets from hypertensives had slower desensitization than those from normotensives. Binding studies at different temperatures and with varying sodium concentrations found no thermodynamic or sodium-dependent differences between normotensive and hypertensive groups. These studies demonstrate that platelets from hypertensive subjects exhibit a defect in the ability of physiological concentrations of agonist to desensitize the alpha 2-adrenoreceptor.

Full text

PDF
1416

Selected References

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

  1. Aragon-Birlouez I., Montenay-Garestier T., Devynck M. A. Further analysis of cell membrane changes in genetic hypertension in rats by diphenylhexatriene fluorescence polarization. Clin Sci (Lond) 1984 Jun;66(6):717–723. doi: 10.1042/cs0660717. [DOI] [PubMed] [Google Scholar]
  2. Awad J. A., Johnson R. A., Jakobs K. H., Schultz G. Interactions of forskolin and adenylate cyclase. Effects on substrate kinetics and protection against inactivation by heat and N-ethylmaleimide. J Biol Chem. 1983 Mar 10;258(5):2960–2965. [PubMed] [Google Scholar]
  3. Bianchi G., Ferrari P., Trizio D., Ferrandi M., Torielli L., Barber B. R., Polli E. Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link. Hypertension. 1985 May-Jun;7(3 Pt 1):319–325. [PubMed] [Google Scholar]
  4. Boon N. A., Elliott J. M., Davies C. L., Conway F. J., Jones J. V., Grahame-Smith D. G., Sleight P. Platelet alpha-adrenoreceptors in borderline and established essential hypertension. Clin Sci (Lond) 1983 Aug;65(2):207–208. doi: 10.1042/cs0650207. [DOI] [PubMed] [Google Scholar]
  5. Brodde O. E., Anlauf M., Graben N., Bock K. D. In vitro and in vivo down-regulation of human platelet alpha 2-adrenoceptors by clonidine. Eur J Clin Pharmacol. 1982;23(5):403–409. doi: 10.1007/BF00605989. [DOI] [PubMed] [Google Scholar]
  6. DOYLE A. E., FRASER J. R., MARSHALL R. J. Reactivity of forearm vessels to vasoconstrictor substances in hypertensive and normotensive subjects. Clin Sci. 1959 Aug;18:441–454. [PubMed] [Google Scholar]
  7. Davies I. B., Sudera D., Sever P. S. Endogenous agonist regulation of alpha-adrenoceptors in man. Clin Sci (Lond) 1981 Dec;61 (Suppl 7):207s–210s. doi: 10.1042/cs061207s. [DOI] [PubMed] [Google Scholar]
  8. De Lean A., Hancock A. A., Lefkowitz R. J. Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes. Mol Pharmacol. 1982 Jan;21(1):5–16. [PubMed] [Google Scholar]
  9. Feldman R. D., Limbird L. E., Nadeau J., FitzGerald G. A., Robertson D., Wood A. J. Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines. J Clin Invest. 1983 Jul;72(1):164–170. doi: 10.1172/JCI110954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feldman R. D., Limbird L. E., Nadeau J., Robertson D., Wood A. J. Leukocyte beta-receptor alterations in hypertensive subjects. J Clin Invest. 1984 Mar;73(3):648–653. doi: 10.1172/JCI111255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goldstein D. S. Arterial baroreflex sensitivity, plasma catecholamines, and pressor responsiveness in essential hypertension. Circulation. 1983 Aug;68(2):234–240. doi: 10.1161/01.cir.68.2.234. [DOI] [PubMed] [Google Scholar]
  12. Goldstein D. S. Plasma norepinephrine in essential hypertension. A study of the studies. Hypertension. 1981 Jan-Feb;3(1):48–52. doi: 10.1161/01.hyp.3.1.48. [DOI] [PubMed] [Google Scholar]
  13. Grimm M., Weidmann P., Keusch G., Meier A., Glück Z. Norepinephrine clearance and pressor effect in normal and hypertensive man. Klin Wochenschr. 1980 Nov 3;58(21):1175–1181. doi: 10.1007/BF01478873. [DOI] [PubMed] [Google Scholar]
  14. Hollister A. S., FitzGerald G. A., Nadeau J. H., Robertson D. Acute reduction in human platelet alpha 2-adrenoreceptor affinity for agonist by endogenous and exogenous catecholamines. J Clin Invest. 1983 Oct;72(4):1498–1505. doi: 10.1172/JCI111106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Limbird L. E., Speck J. L., Smith S. K. Sodium ion modulates agonist and antagonist interactions with the human platelet alpha 2-adrenergic receptor in membrane and solubilized preparations. Mol Pharmacol. 1982 May;21(3):609–617. [PubMed] [Google Scholar]
  16. McGregor L., Morazain R., Renaud S. Platelet functions and fatty acid composition of platelet phospholipids in spontaneously hypertensive rats fed saturated or polyunsaturated fats. Atherosclerosis. 1981 Jan-Feb;38(1-2):129–136. doi: 10.1016/0021-9150(81)90110-6. [DOI] [PubMed] [Google Scholar]
  17. Michel T., Hoffman B. B., Lefkowitz R. J. Differential regulation of the alpha 2-adrenergic receptor by Na+ and guanine nucleotides. Nature. 1980 Dec 25;288(5792):709–711. doi: 10.1038/288709a0. [DOI] [PubMed] [Google Scholar]
  18. Motulsky H. J., Insel P. A. Influence of sodium on the alpha 2-adrenergic receptor system of human platelets. Role for intraplatelet sodium in receptor binding. J Biol Chem. 1983 Mar 25;258(6):3913–3919. [PubMed] [Google Scholar]
  19. Motulsky H. J., O'Connor D. T., Insel P. A. Platelet alpha 2-adrenergic receptors in treated and untreated essential hypertension. Clin Sci (Lond) 1983 Mar;64(3):265–272. doi: 10.1042/cs0640265. [DOI] [PubMed] [Google Scholar]
  20. Nara Y., Kihara M., Nabika T., Mano M., Horie R., Yamori Y. Dietary effect on platelet aggregation in men with and without a family history of essential hypertension. Hypertension. 1984 May-Jun;6(3):339–343. doi: 10.1161/01.hyp.6.3.339. [DOI] [PubMed] [Google Scholar]
  21. Pittman R. N., Molinoff P. B. Interactions of agonists and antagonists with beta-adrenergic receptors on intact L6 muscle cells. J Cyclic Nucleotide Res. 1980;6(6):421–435. [PubMed] [Google Scholar]
  22. Postnov I. V. Gipertonicheskaia bolezn' kak membrannai patologiia. Kardiologiia. 1975 Aug;15(8):18–23. [PubMed] [Google Scholar]
  23. Robertson D., Goldberg M. R., Hollister A. S., Wade D., Robertson R. M. Clonidine raises blood pressure in severe idiopathic orthostatic hypotension. Am J Med. 1983 Feb;74(2):193–200. doi: 10.1016/0002-9343(83)90607-1. [DOI] [PubMed] [Google Scholar]
  24. Robertson D., Hollister A. S., Carey E. L., Tung C. S., Goldberg M. R., Robertson R. M. Increased vascular beta2-adrenoceptor responsiveness in autonomic dysfunction. J Am Coll Cardiol. 1984 Mar;3(3):850–856. doi: 10.1016/s0735-1097(84)80264-8. [DOI] [PubMed] [Google Scholar]
  25. Robertson D., Johnson G. A., Robertson R. M., Nies A. S., Shand D. G., Oates J. A. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation. 1979 Apr;59(4):637–643. doi: 10.1161/01.cir.59.4.637. [DOI] [PubMed] [Google Scholar]
  26. Robertson D., Shand D. G., Hollifield J. W., Nies A. S., Frölich J. C., Oates J. A. Alterations in the responses of the sympathetic nervous system and renin in borderline hypertension. Hypertension. 1979 Mar-Apr;1(2):118–124. doi: 10.1161/01.hyp.1.2.118. [DOI] [PubMed] [Google Scholar]
  27. Vlachakis N. D., Aledort L. Platelet aggregation in relationship to plasma catecholamines in patients with hypertension. Atherosclerosis. 1979 Apr;32(4):451–460. doi: 10.1016/0021-9150(79)90011-x. [DOI] [PubMed] [Google Scholar]
  28. Vlachakis N. D. Blood pressure response to norepinephrine infusion in relationship to plasma catecholamines and renin activity in man. J Clin Pharmacol. 1979 Oct;19(10):654–661. doi: 10.1002/j.1552-4604.1979.tb01628.x. [DOI] [PubMed] [Google Scholar]
  29. Weidmann P., Grimm M., Meier A., Glück Z., Keusch G., Minder I., Beretta-Piccoli C. Pathogenic and therapeutic significance of cardiovascular pressor reactivity as related to plasma catecholamines in borderline and established essential hypertension. Clin Exp Hypertens. 1980;2(3-4):427–449. doi: 10.3109/10641968009037123. [DOI] [PubMed] [Google Scholar]
  30. Weiland G. A., Minneman K. P., Molinoff P. B. Thermodynamics of agonist and antagonist interactions with mammalian beta-adrenergic receptors. Mol Pharmacol. 1980 Nov;18(3):341–347. [PubMed] [Google Scholar]
  31. Weiss R. J., Smith C. B. Altered platelet alpha 2-adrenoceptors in patients with angina pectoris. J Am Coll Cardiol. 1983 Oct;2(4):631–637. doi: 10.1016/s0735-1097(83)80302-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES