Central Endogenous Endothelins (ETs) are Involved in the DOCA-Salt Hypertension. Interactions Between ETs Receptor A (ETA) Blockade and Tyrosine Hydroxylase (TH) in the Anterior (AH) and Posterior Hypothalamus (PH)

CASSINOTTI L.; VATTA M.; MORALES V.; BIANCIOTTI L.; GUIL M.; ÁLVAREZ C.

Savannah, Georgia

Conferencia; 2015 APS Conference: 14th International Conference on Endothelin Physiology, Pathophysiology and Therapeutics; 2016

The American Physiological Society

In previous studies we have reported that the exogenous administration of ETs modifiednoradrenergic transmission in PH and AH of DOCA-salt hypertensive rats.Therefore in the present work we sought to establish the role of ETA receptor stimulationby endogenous ETs and its correlation with TH activity and expression in theAH and PH of DOCA-salt hypertensive rats. Normotensive and DOCA-salt hypertensiveSprague-Dawley male rats were prepared with a guide cannula placed in thebrain lateral ventricle for the administration of artificial cerebrospinal fluid (CSFa) orBQ610 (ETA receptor antagonist). Following a recovery period of seven days, bothgroups were randomly sub-divided and icv administered with 1ul CSFa or 1ulBQ610 (20mM). BP was monitored for 60 min through a catheter placed in thefemoral artery. Brain was then removed and the AH and PH dissected. The expressionof TH and its phosphorylated forms were determined by immunoblottingand TH activity by a radioenzymatic assay. Results showed that BQ610 markedly reducedblood pressure in both normotensive and hypertensive animals, although amore prominent decrease was observed in systolic BP of DOCA-salt hypertensiverats (30 mmHg decrease following 30 min ETA exposure). No changes in TH expressionor activity was observed in the PH and AH of normotensive rats either injectedwith vehicle or BQ610, or in the AH of DOCA-salt hypertensive rats. Howeverin hypertensive rats PH, ETA blockade reduced TH phosphorylation at 40Serand 19Ser sites (55.6% and 33.3%, respectively). Moreover, a Pearson correlationindex showed that the amount of TH and TH-PSer40 expressed in this region correlatedwith SBP values (p