Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats

CASSINOTTI, LUIS; GUIL, MARÍA; SCHÖLLER, MERCEDES; NAVARRO, MONICA; BIANCIOTTI, LILIANA G; VATTA, MARCELO

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2018 vol. 19

1422-0067

Abstract: Overactivity of the sympathetic nervous system and central endothelins (ETs) areinvolved in the development of hypertension. Besides the well-known brain structures involvedin the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggeststhat the olfactory bulb (OB) also modulates cardiovascular function. In the present study, weevaluated the interaction between the endothelinergic and catecholaminergic systems in the OB ofdeoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ETA)blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changesin tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensiverats. Time course variations in systolic blood pressure and heart rate were also registered. Resultsshowed that ETA blockade dose dependently reduced blood pressure in hypertensive rats, but itdid not change heart rate. It also prevented the increase in TH activity and expression (mRNAand protein) in the right OB of hypertensive animals. However, ETA blockade did not affecthemodynamics or TH in normotensive animals. Present results support that brain ETA are notinvolved in blood pressure regulation in normal rats, but they significantly contribute to chronicblood pressure elevation in hypertensive animals. Changes in TH activity and expression wereobserved in the right but not in the left OB, supporting functional asymmetry, in line with previousstudies regarding cardiovascular regulation. Present findings provide further evidence on therole of ETs in the regulation of catecholaminergic activity and the contribution of the right OB toDOCA-salt hypertension.