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

• Published in: European journal of pharmacology Vol. 885; p. 173543
• Main Authors: Guil, María J, Soria, Celeste, Seijas, Mayra, Bianciotti, Liliana G, Vatta, Marcelo S
• Format: Journal Article
• Language: English
• Published: Netherlands 15-10-2020
• Subjects: Animals; Blood Pressure - drug effects; Desoxycorticosterone; Endothelins - pharmacology; Heart Rate - drug effects; Hypertension - chemically induced; Hypertension - drug therapy; Hypertension - physiopathology; Male; Nitric Oxide Synthase Type I - biosynthesis; Nitric Oxide Synthase Type I - genetics; Olfactory Bulb - drug effects; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B - agonists; RNA, Messenger - biosynthesis; Sympathetic Nervous System - drug effects; Hypertension; Central nervous system; Endothelin-1; Catecholamines; Olfactory bulb; Endothelin ET(B) receptor
• ISSN: 1879-0712

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.