Former data of our workgroup indicated that the accumulation of oxidized amino acids
(meta- and ortho-tyrosine) due to oxidative stress may play an important role in the impaired insulininduced
vasoactive properties of different arterial segments. There are evidences, that incorporation of
these amino acids into cellular proteins leads to certain hormonal resistances, which might be restored
by supplementation with the physiologic isoform, para-tyrosine.
Rats in the control group were kept on a regular diet, rats in the cholesterol-fed group received high-fat diet, while the
third group of rats received high-fat diet with para-tyrosine supplementation for 16 weeks. Plasma cholesterol level was
significantly higher in the cholesterol-fed group, while the level of cholesterol in the cholesterol+para-tyrosine group did
not differ significantly from that of the controls. Plasma level of insulin after glucose stimulation was decreased in the
cholesterol-fed group, while that in the para-tyrosine supplemented group did not differ significantly from the controls.
Vascular para-, meta- and ortho-tyrosine content was measured with HPLC. Elevated vascular meta-tyrosine/para-tyrosine
ratio of cholesterol fed rats could be avoided by para-tyrosine supplementation. Vascular response of the thoracic aorta to
insulin and liraglutide was assessed by a DMT multi-myograph. Cholesterol feeding resulted in vascular insulin-and
liraglutide resistance, which was restored by para-tyrosine supplementation.
Incorporation of the oxidative stress induced pathological tyrosine isoforms leads to vascular-hormone-resistances. We
show that the physiological amino acid para-tyrosine is capable of restoring hypercholesterolemia-induced increased
meta-tyrosine content of the vascular wall, thus attenuating functional vascular damage.