Enhanced Assymetrical Noradrenergic Transmission in the Olfactory Bulb of Deoxycorticosterone Acetate-Salt Hypertensive Rats

Abstract

The ablation of olfactory bulb induces critical changes in dopamine, and monoamine oxidase activity in the brain stem. Growing evidence supports the participation of this telencephalic region in the regulation blood pressure and cardiovascular activity but little is known about its contribution to hypertension. We have previously reported that in the olfactory bulb of normotensive rats endothelins enhance noradrenergic activity by increasing tyrosine hydroxylase activity and norepinephrine release. In the present study we sought to establish the status of noradrenergic activity in the olfactory bulb of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Different steps in norepinephrine transmission including tyrosine hydroxylase activity, neuronal norepinephrine release and uptake were assessed in the left and right olfactory bulb of DOCA-salt hypertensive rats. Increased tyrosine hydroxylase activity, and decreased neuronal norepinephrine uptake were observed in the olfactory bulb of DOCA-salt hypertensive rats. Furthermore the expression of tyrosine hydroxylase and its phosphorylated forms were also augmented. Intriguingly, asymmetrical responses between the right and left olfactory bulb of normotensive and hypertensive rats were observed. Neuronal norepinephrine release was increased in the right but not in the left olfactory bulb of DOCA-salt hypertensive rats, whereas non asymmetrical differences were observed in normotensive animals. Present findings indicate that the olfactory bulb of hypertensive rats show an asymmetrical increase in norepinephrine activity. The observed changes in noradrenergic transmission may likely contribute to the onset and/or progression of hypertension in this animal model.

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

“…TH has four potential phosphorylation Ser-sites, three of which are intimately implicated in the activity of the enzyme (Ser19, Ser31 and Ser 40). Consistent with previous studies, the expression of TH-PSer19, TH-PSer31 and TH-PSer40 were increased in the OB of DOCA-Salt rats [14]. Blockade of ET A by BQ610, decreased the expression of the phosphorylated forms of the enzyme to control levels in hypertensive animals but induced no changes in normotensive rats (Figures 4c and 4d).…”

“…TH activity was enhanced in the OB of hypertensive animals as previously reported [14]. Blockade of ET A induced no changes in TH activity in normotensive animals, but it reduced the enzyme activity to control values in DOCA-Salt hypertensive rats (Figure 4a).…”

“…Changes in rat vascular and cardiac physiology correlate with norepinephrine (NE) levels in the OB, suggesting that olfactory stimulation enhances sympathetic activity and blood pressure through a multisynaptic pathway connecting the OB with brain autonomic centers [6,13]. Recent studies from our laboratory show that catecholaminergic transmission in the OB is enhanced DOCA-Salt hypertensive rats [14]. Despite growing evidence, the role of the OB in the regulation of cardiovascular function has not been fully established [15,16].…”

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

“…In a later study, we reported that long-term exposure to ETs enhances TH mRNA and the expression of total TH and its phosphorylation forms in normotensive rats [ 14 ]. Furthermore, to our knowledge, we were the first to report that in the right OB of DOCA-salt hypertensive rats TH activity and expression as well as neuronal norepinephrine release were increased whereas the uptake of the amine was diminished [ 40 ].…”

“…In the left OB, the catecholaminergic activity was unchanged. We previously reported an asymmetrical behavior in the OB of DOCA-salt rats and non-asymmetrical differences in normotensive animals [ 40 ]. The existence of brain asymmetry, including norepinephrine levels in the hypothalamus, has been reported in distinct animal species [ 45 ].…”