Title:Role of Brain Endothelin Receptor Type B (ETB) in the Regulation of
Tyrosine Hydroxylase in the Olfactory Bulb of DOCA-Salt Hypertensive
Rats
Volume: 21
Issue: 4
Author(s): Luis Cassinotti, María Guil, Liliana Bianciotti and Marcelo Vatta*
Affiliation:
- Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
- Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
Keywords:
Hypertension, endothelin, olfactory bulb, central nervous system, DOCA-salt, tyrosine hydroxylase, endothelin receptor type B.
Abstract:
Background: We previously reported that endothelins (ETs) regulate tyrosine hydroxylase
(TH) activity and expression in the olfactory bulb (OB) of normotensive and hypertensive animals.
Applying an ET receptor type A (ETA) antagonist to the brain suggested that endogenous ETs bind to
ET receptor type B (ETB) to elicit effects.
Objective: The aim of the present work was to evaluate the role of central ETB stimulation on the regulation
of blood pressure (BP) and the catecholaminergic system in the OB of deoxycorticosterone acetate
(DOCA)-salt hypertensive rats.
Methods: DOCA-salt hypertensive rats were infused for 7 days with cerebrospinal fluid or IRL-1620
(ETB receptor agonist) through a cannula placed in the lateral brain ventricle. Systolic BP (SBP) and
heart rate were recorded by plethysmography. The expression of TH and its phosphorylated forms in the
OB were determined by immunoblotting, TH activity by a radioenzymatic assay, and TH mRNA by
quantitative real-time polymerase chain reaction.
Results: Chronic administration of IRL-1620 decreased SBP in hypertensive rats but not in
normotensive animals. Furthermore, the blockade of ETB receptors also decreased TH-mRNA in
DOCA-salt rats, but it did not modify TH activity or protein expression.
Conclusion: These findings suggest that brain ETs through the activation of ETB receptors contribute to
SBP regulation in DOCA-salt hypertension. However, the catecholaminergic system in the OB does not
appear to be conclusively involved although mRNA TH was reduced. Present and previous findings
suggest that in this salt-sensitive animal model of hypertension, the OB contributes to chronic BP
elevation.