INVESTIGADORES
VATTA Marcelo Sergio
congresos y reuniones científicas
Título:
Central Endogenous Endothelins (ETs) are Involved in the DOCA-Salt Hypertension. Inter- actions Between ETs Receptor A (ETA) Blockade and Tyrosine Hydroxylase (TH) in the Anterior (AH) and Posterior Hypothalamus (PH).
Autor/es:
GUIL MJ; MORALES VP; CASSINOTTI L; ALVAREZ CD; BIANCIOTTI LG; VATTA MS
Lugar:
Savannah
Reunión:
Conferencia; 2015 APS /ET- 14: International Conference on Endothelin: Physiology, Pathophysiology and Therapeutics; 2015
Institución organizadora:
American Physiological Society
Resumen:
In previous studies we have reported that theexogenous administration of ETs modified noradrenergic transmission in PH andAH of DOCA-salt hypertensive rats. Therefore in the present work we sought toestablish the role of ETA receptor stimulation by endogenous ETs and itscorrelation with TH activity and expression in the AH and PH of DOCA-salthypertensive rats. Normotensive and DOCA-salt hypertensive Sprague-Dawley malerats were prepared with a guide cannula placed in the brain lateral ventriclefor the administration of artificial cerebrospinal fluid (CSFa) or BQ610 (ETAreceptor antagonist). Following a recovery period of seven days, both groupswere randomly sub-divided and icv administered with 1ul CSFa or 1ul BQ610(20mM). BP was monitored for 60 min through a catheter placed in the femoralartery. Brain was then removed and the AH and PH dissected. The expression ofTH and its phosphorylated forms were determined by immunoblotting and THactivity by a radioenzymatic assay. Results showed that BQ610 markedly reducedblood pressure in both normotensive and hypertensive animals, although a moreprominent decrease was observed in systolic BP of DOCA-salt hypertensive rats(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. However inhypertensive rats PH, ETA blockade reduced TH phosphorylation at 40Ser and19Ser sites (55,6% and 33.3%, respectively). Moreover, a Pearson correlationindex showed that the amount of TH and TH-PSer40 expressed in this regioncorrelated with SBP values (p<0.05). These results were in accordance withincreased ETA expression (129%, p<0.05) found in the HP of DOCA-salt rats.Present findings shows that ETA receptor blockade reduces catecholamineactivity in the PH of DOCA-salt hypertensive rats. Given that the PH is awell-characterized sympatho-excitatory area intimately involved in theregulation of cardiovascular activity it can conclude that brain ETs throughETA receptor activation strongly contribute to blood pressure elevation inDOCA-salt hypertension. These findings further support the relevance of thecentral nervous system in the development of hypertension in this animal model.