Role of endothelin receptor type A on catecholamine regulation in the olfactory bulb of DOCA-salt hypertensive rats: Hemodynamic implications

Biochim Biophys Acta Mol Basis Dis. 2019 Nov 1;1865(11):165527. doi: 10.1016/j.bbadis.2019.08.003. Epub 2019 Aug 6.

Abstract

Increasing evidence shows that the olfactory bulb is involved in blood pressure regulation in health and disease. Enhanced noradrenergic transmission in the olfactory bulb was reported in hypertension. Given that endothelins modulate catecholamines and are involved in the pathogenesis of hypertension, in the present study we sought to establish the role of the endothelin receptor type A on tyrosine hydroxylase, the rate limiting enzyme in catecholamine biosynthesis, in the olfactory bulb of DOCA-salt hypertensive rats. Sprague-Dawley male rats, randomly divided into Control and DOCA-Salt hypertensive groups, were used to assess endothelin receptors by Western blot and confocal microscopy, and their co-localization with tyrosine hydroxylase in the olfactory bulb. Blood pressure and heart rate as well as tyrosine hydroxylase expression and activity were assessed following BQ610 (ETA antagonist) applied to the brain. DOCA-Salt hypertensive rats showed enhanced ETA and decreased ETB expression. ETA co-localized with tyrosine hydroxylase positive neurons. Acute ETA blockade reduced blood pressure and heart rate and decreased the expression of total tyrosine hydroxylase and its phosphorylated forms. Furthermore, it also diminished mRNA tyrosine hydroxylase expression and accelerated the enzyme degradation through the proteasome pathway as shown by pretreatment with MG132, (20s proteasome inhibitor) intracerebroventricularly applied. Present findings support that the brain endothelinergic system plays a major role through ETA activation in the increase of catecholaminergic activity in the olfactory bulb of DOCA-Salt hypertensive rats. They provide rationale evidence that this telencephalic structure contributes in a direct or indirect way to the hemodynamic regulation in salt dependent hypertension.

Keywords: DOCA-salt rats; Endothelin; Endothelin receptors; Experimental hypertension; Olfactory bulb; Tyrosine hydroxylase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Catecholamines / metabolism*
  • Desoxycorticosterone Acetate / adverse effects
  • Hemodynamics
  • Hypertension / etiology
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A / analysis
  • Receptor, Endothelin A / metabolism*

Substances

  • Catecholamines
  • Receptor, Endothelin A
  • Desoxycorticosterone Acetate