Objective: Since detyrosinated tubulin (Glu-Tub) is increased in the membranes of hypertensive erythrocytes and a reduced content and activity of the enzyme tubulin tyrosine ligase (TTL) in erythrocytes from hypertensive individuals with respect to normotensive individuals was reported, role of TTL in hypertension development was analysed. Methods: Erythrocytes and brain of 4 and 10-week-old spontaneously hypertensive rats (SHR) and their normotensive Wistar controls were used to determine content and distribution of tubulin and TTL by immunoblot and immunofluorescence, respectively. TTL activity was determined by incorporation of 14 CTyrosine in tubulin. Moreover, arterial pressure and erythrocyte deformability was determined after treatment of animals with tyrosine and 3-NO 3 -tyrosine as substrates of TTL. Results: Results show that the content and enzymatic activity of erythrocyte TTL remain constant in SHR rats in their prehypertensive 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. Moreover, decrease in Glu-Tub in the erythrocyte membrane in SHR rats treated with tyrosine or 3-NO 3 -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. Conclusion: 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.
Santander et al. (Tue,) studied this question.