Increased content of tubulin tyrosin ligase is essential to maintaining normal arterial pressure: preventive effect of tyrosine and NO3-tyrosine on hypertension development.

SANTANDER V; MONESTEROLO NE; BALACH M.; A NIGRA; RIVELLI JF; CAMPETELLI A.N; CASALE C. H.

Mendoza

Congreso; SAIB 2022; 2023

SAIB

We previously showed that detyrosinated tubulin (Glu-Tub) is increased in the membranes of hypertensive erythrocytes. In addition, we reported reduced content and activity of the enzyme tubulin tyrosine ligase (TTL) in erythrocytes from hypertensive subjects with respect to normotensive subjects. Now, we show that the content and enzymatic activity of erythrocyte TTL remain constant in SHR rats in their pre-hypertensive stage until the pathology develops, while normotensive rats increase both the activity and the amount of TTL throughout their lives. This is consistent with an increase in Glu-Tub in SHR membranes with developed hypertension compared to normotensive rats. We also show that the decrease in Glu-Tub in the erythrocyte membrane in SHR rats, treated with tyrosine or 3-NO3-tyrosine as TTL substrates, partially reverses the low deformability of their erythrocytes and high blood pressure caused by the high content of Glu-Tub in the membrane. The results suggest that alterations in the tubulin tyrosination/detyrosination cycle are involved in biochemical and rheological changes in the blood of hypertensive subjects and,consequently, in the development of hypertension.