Central chronic blockade of ETA receptors decreases hypothalamic catecholaminergic activity and reduces blood pressure in DOCA-salt hypertensive rats

MERCEDES SCHOLLER; MARIA JULIA GUIL; MARCELO S. VATTA; LUIS CASSINOTTI; LILIANA G. BIANCIOTTI

Praga

Congreso; The Fifteenth International Conference on Endothelin; 2017

The central nervous system is involved in the short-term regulation of blood pressure although increasing evidence supports that it also participates in its long-term modulation and eventual development of hypertension. In the present study, we assessed the effect of central blockade of ETA receptors by the specific antagonist BQ-610 for 7 days on the expression, phosphorylation and activity of tyrosine hydroxylase in the anterior and posterior hypothalamus of normotensive and DOCA-salt hypertensive rats. We further analyzed the effect on systolic blood pressure and the development of cardiac hypertrophy. Results showed that in the anterior hypothalamus of DOCA-salt hypertensive rats there was a decrease in the mRNA, protein level, phosphorylation and activity of tyrosine hydroxylase. However, opposite effects on the enzyme were observed in the posterior hypothalamus. Chronic blockade of ETA receptors not only prevented tyrosine hydroxylase changes in the hypothalamus but it also decreased systolic blood pressure and cardiac hypertrophy in DOCA-salt rats. These findings show that the reduction of catecholaminergic activity in the hypothalamus by chronic ETA blockade decreases blood pressure in DOCA-salt hypertensive rats and further suggest that ETA receptors play a key role the development of hypertension in this animal model.