Central endothelin ET receptor activation reduces blood pressure and catecholaminergic activity in the olfactory bulb of deoxycorticosterone acetate-salt hypertensive rats.

Endothelins regulate catecholaminergic activity in the olfactory bulb (OB) in normotensive and hypertensive animals. Administration of an endothelin ET receptor antagonist decreases blood pressure in deoxycorticosterone acetate-salt (DOCA-salt) rats along with a reduction in tyrosine hydroxylase (TH) activity and expression. In the present work, we sought to establish the role of brain endothelin ET receptor on blood pressure regulation and its relationship with the catecholaminergic system within the OB of DOCA-Salt rats. Sprague-Dawley male rats were divided into control and DOCA-Salt groups. Blood pressure, heart rate and TH activity as well as neuronal nitric oxide synthase (nNOS) expression were assessed following IRL-1620 (selective endothelin ET receptor agonist) applied to be brain. IRL-1620 significantly reduced systolic, diastolic, and mean arterial pressure in DOCA-Salt hypertensive rats. It also decreased TH activity, TH total and phosphorylated forms expression as well as its mRNA in the OB of hypertensive animals. The expression of phospho-Ser1417-nNOS, which reflects nNOS activation, was significantly decreased in the of OB of DOCA-salt rats, but it was enhanced by IRL-1620. These findings suggest that DOCA-Salt hypertension depends on endogenous central endothelin ET receptor activity, rather than on ET, and that low endothelin ET stimulation is essential for blood pressure elevation in this animal model. The effect of endothelin ET receptor antagonism may also result from endothelin ET receptor overstimulation. The present study shows that endothelin receptors are involved in the regulation of TH in the OB and that such changes are likely implicated in the hemodynamic control and sympathetic outflow.