Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat

Abstract

New Findings What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity‐dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast‐cyclic voltammetry, we found that changes in local tissue PnormalO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation‐induced changes in local tissue PnormalO2 (PnormaltO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PnormaltO2 were performed using a novel application of fast‐cyclic voltammetry, which allows higher temporal resolution of O2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PnormaltO2 in the cNTS, characterized by a rapid decrease in PnormaltO2 (‘initial dip’) followed by a post‐stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post‐ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In conclusion, neural activity‐dependent changes in tissue oxygen in brainstem cardiovascular autonomic centres are significantly impaired in animals with arterial hypertension.

Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans

“…However, since intracellular PO 2 in these cells are likely to be considerably lower than the ambient (256,328,445,692). In these studies, stimulation of neuronal activity was associated with a transient reduction in tissue PO 2 , likely representing localized increases in O 2 consumption, followed by increases in local blood PO 2 and flow, confirming similar observations using fMRI.…”

Electrochemical carbon fiber-based technique for simultaneous recordings of brain tissue PO2, pH, and extracellular field potentials

“…Animals were anaesthetised and instrumented as described above (Figure 1A). In this set of experiments the dorsal surface of the brainstem was exposed for CFM recordings as previously described (Hosford et al 2015; Hosford et al 2017). The left cervical vagus nerve was exposed, separated from the sympathetic trunk and placed on the bipolar silver wire electrodes for electrical stimulation (800 μA, 1 ms at 3 Hz).…”

“…The sub-second time resolution of FCV allows detection of events that occur at the onset of neuronal activity and precede increases in blood flow (Logothetis et al 2001). Separate electrochemical detection of tissue partial pressure of oxygen (PtO 2 ) and pH using FCV has been achieved previously (Bucher et al 2014; Hosford et al 2017; Takmakov et al 2010). Here we describe a novel FCV-based technique that enables simultaneous recordings of key variables representing the metabolic state of the brain: brain tissue PO 2 , pH and neuronal activity.…”

Electrochemical carbon fiber-based technique for simultaneous recordings of brain tissue PO2, pH, and extracellular field potentials

“…Animals were anaesthetised and instrumented as described above. In this set of experiments the dorsal surface of the brainstem was exposed for CFM recordings as previously described ( Hosford et al, 2015 , Hosford et al, 2017 ). The left cervical vagus nerve was exposed, separated from the sympathetic trunk and placed on the bipolar silver wire electrodes for electrical stimulation (800 μA, 1 ms at 3 Hz).…”

“…The sub-second time resolution of FCV allows detection of events that occur at the onset of the neuronal activity and precede increases in blood flow. Separate electrochemical detection of tissue partial pressure of oxygen (P t O 2 ) and pH using FCV had been achieved previously ( Bucher et al, 2014 ; Hosford et al, 2017 ; Takmakov et al, 2010 ). Here we describe a novel FCV-based technique that enables simultaneous recordings of key variables representing the metabolic state of the brain: brain tissue PO 2 , pH and neuronal activity.…”