title: Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat.
abstract: 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 PO2 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 PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast-cyclic voltammetry, which allows higher temporal resolution of O2changes 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 PtO2 in the cNTS, characterized by a rapid decrease in PtO2 ('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.
authors.affiliation: Center for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Hosford
authors.affiliation: Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Millar
authors.affiliation: Center for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Ramage
authors.affiliation: Center for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.|Clinical Pharmacology and Experimental Therapeutics, Division of Medicine, University College London, London, UK.
authors.forename: Nephtali
authors.identifier: 0000-0001-9921-660X
authors.initials: N
authors.lastname: Marina
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D010100:Oxygen
keywords: arterial hypertension; brainstem; neurovascular coupling