Journal of Neural Transmission

, Volume 66, Issue 2, pp 121–128 | Cite as

Acute effects of aspartame on systolic blood pressure in spontaneously hypertensive rats

  • P. J. Kiritsy
  • T. J. Mäher
Original Papers


Exogenous tyrosine lowers blood pressure in spontaneously hypertensive rats (SHR). The artificial sweetener aspartame also elevates blood and brain tyrosine levels in rats by being hydrolyzed to phenylalanine, which is then rapidly hydroxylated to tyrosine in the liver. Hence we tested the ability of aspartame; its hydrolytic products phenylalanine, aspartic acid and methanol; and of tyrosine itself to lower blood pressure in SHR. For one week prior to experimentation rats were acclimated to the indirect blood pressure measurement technique; on the day of an experiment they received I.P. injections (mg/kg) of aspartame (12.5–200), tyrosine (25–200) or phenylalanine (100–200), or of aspartic acid or methanol in the doses theoretically contained within 200 mg/kg aspartame. Animals receiving 50, 100 or 200 mg/kg of aspartame exhibited maximum falls in blood pressure of 17.3, 24.2 and 19.3 mmHg, respectively. All changes were significant, as determined by ANOVA and the Newman-Keuls test (p<0.05). Tyrosine or phenylalanine also lowered blood pressure, but aspartic acid or methanol produced no significant effects. Co-administration of aspartame with valine, a large neutral amino acid that competes with phenylalanine or tyrosine for brain uptake, attenuated aspartame's hypotensive effect. These observations suggest that the neurochemical changes produced by aspartame lead to predicted tyrosine-induced changes in blood pressure.

Key words

Aspartame blood pressure SHR tyrosine hypertension brain 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aragon MC, Gimenez C, Valdivieso F (1982) Inhibition of L-phenylalanine of tyrosine transport by synaptosomal plasma membrane vesicles: Implication in the pathogenesis of phenylketonuria. J Neurochem 39: 1185–1187Google Scholar
  2. Bresnahan MR, Hatzinikolaw P, Brunner HR, Gavras R (1980) Effect of tyrosine infusion in normotensive and hypertensive rats. Am J Physiol 239: H 206Google Scholar
  3. Conlay LA, Mäher TJ, Wurtman RJ (1981) Tyrosine increases blood pressure in hypotensive rats. Science 212: 559–560Google Scholar
  4. Coulombe RA, Raghubir SP (1985) Neurobiochemical alterations induced by the sweeter aspartame (Nutrasweet). J Appl Environ Tox, in pressGoogle Scholar
  5. El Mestikaway S, Glowinski J, Hamon M (1983) Tyrosine hydroxylase activation in depolarized dopaminergic terminals-involvement of Ca+2-dependent phosphorylation. Nature 302: 830–832Google Scholar
  6. Federal Register (1974) 39: 27317 July 26Google Scholar
  7. Federal Register (1983) 48: 31376 July 8Google Scholar
  8. Fernstrom JD, Fernstrom MH, Gillis MA (1983) Acute effects of aspartame on large neutral amino acids and monoamines in rat brain. Life Sci 32: 1651–1658Google Scholar
  9. Glaeser BS, Maher TJ, Wurtman RJ (1983) Changes in brain levels of acid, basic, and neutral amino acids after consumption of single meals containing various proportions of protein. J Neurochem 41 (4): 1016–1021Google Scholar
  10. Grobelny D, Galardy RE (1985) A metabolite of aspartame inhibits angiotensin converting enzyme. Biochem Biophys Res Commun 128 (2): 960–964Google Scholar
  11. Lovenberg W, Bruckwick EA, Hanbauer I (1975) ATP, cyclic AMP, and magnesium increase the affinity of rat striatal tyrosine hydroxylase for its cofactor. Proc Natl Acad Sci U.S.A. 72: 2955–2958Google Scholar
  12. Maher TJ, Wurtman RJ (1983) High doses of aspartame reduce blood pressure in spontaneously hypertensive rats. N Engl J Med 309: 1125Google Scholar
  13. Maher TJ, Glaeser BS, Wurtman RJ (1984) Diurnal variations in plasma concentrations of basic and neutral amino acids and in red cell concentrations of aspartate and glutamate: effects of dietary protein intake. Am J Clin Nutr 39: 722–729Google Scholar
  14. Mandel AJ (1978) Redundant mechanisms regulating brain tyrosine and tryptophan hydroxylases. Annu Rev Pharmacol Toxicol 18: 461–493Google Scholar
  15. Pardridge W (1977). In: Wurtman RJ, Wurtman JJ (eds) Nutrition and the brain, vol 1. Raven Press, New York, pp 141–204Google Scholar
  16. Sved AF, Fernstrom JD, Wurtman RJ (1979) Tyrosine administration reduces blood pressure and enhances norepinephrine release in SHR rats. Proc NatlAcad Sci 76 (7): 3511–3514Google Scholar
  17. Udenfriend S (1976) Guidelines in the breeding and use of spontaneously hypertensive rats (SHR). ILAR News 19: g1-g20Google Scholar
  18. Weiner N, Lee FL, Dreyer E, Barnes E (1978) The activation of tyrosine hydroxylase in noradrenergic neurons during acute nerve stimulation. Life Sci 22: 1119–1216Google Scholar
  19. Wurtman RJ, Hefti F, Melamed E (1981) Precursor control of neurotransmitter synthesis. Pharmacol Rev 32 (4): 315–335Google Scholar
  20. Wurtman RJ (1983) Neurochemical changes following high-dose aspartame with dietary carbohydrates. N Engl J Med 309(7): 429–430Google Scholar
  21. Wurtman RJ (1985) Aspartame: Possible effect on seizure susceptibility. Lancet ii: 1060Google Scholar
  22. Yokogoshi H, Roberts C, Caballero B, Wurtman RJ (1984) Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles. Am J Clin Nutr 40: 1–7Google Scholar
  23. Yokogoshi H, Wurtman RJ (1986) Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain. J Nutr 116: 356–364Google Scholar
  24. Zivin JA, Bartko JJ (1976) Statistics for the disinterested scientist. Life Sci 18: 15–26Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • P. J. Kiritsy
    • 1
  • T. J. Mäher
    • 1
  1. 1.Neuropharmacology Laboratory, Department of PharmacologyMassachusetts College of Pharmacy and Allied Health ScienceBostonUSA

Personalised recommendations