Immunohistochemical evidence of tissue hypoxia and astrogliosis in the rostral ventrolateral medulla of spontaneously hypertensive rats.
Increased activity of the sympathetic nervous system has been highlighted as a key factor that contributes to the development and maintenance of arterial hypertension. However, the factors that precipitate sustained increases in sympathetic activity remain poorly understood. Resting tissue oxygen partial pressure (PtO2) in the brainstem of anesthetized spontaneously hypertensive rats (SHRs) has been shown to be lower than in normotensive rats despite normal levels of arterial PO2. A hypoxic environment in the brainstem has been postulated to activate astroglial signalling mechanisms in the rostral ventrolateral medulla (RVLM) which in turn increase the excitability of presympathetic neuronal networks. In this study, we assessed the expression of indirect markers of tissue hypoxia and astroglial cell activation in the RVLM of SHRs and age-matched normotensive Wistar rats. Immunohistochemical labelling for hypoxia-induced factor-1α (HIF-1α) and bound pimonidazole adducts revealed the presence of tissue hypoxia in the RVLM of SHRs. Double immunostaining showed co-localization of bound pimonidazole labelling in putative presympathetic C1 neurons and in astroglial cells. Quantification of glial fibrillary acidic protein (GFAP) immunofluorescence showed relatively higher number of astrocytes and increased GFAP mean grey value density, whilst semi-quantitative analysis of skeletonized GFAP-immunoreactive processes revealed greater % area covered by astrocytic processes in the RVLM of adult SHRs. In conclusion, the morphological findings of tissue hypoxia and astrogliosis within brainstem presympathetic neuronal networks in the SHR support previous observations, showing that low brainstem PtO2and increased astroglial signalling in the RVLM play an important role in pathological sympathoexcitation associated with the development of arterial hypertension.
Department of Neuroscience, Physiology and Pharmacology, University College London, UK; UCL Centre for Cardiovascular and Metabolic Neuroscience University College London, Gower Street, London WC1E 6BT, UK.
Tymoteusz
T
Turlejski
Department of Neuroscience, Physiology and Pharmacology, University College London, UK; UCL Centre for Cardiovascular and Metabolic Neuroscience University College London, Gower Street, London WC1E 6BT, UK.
Ibrahim
I
Humoud
Department of Neuroinflammation, Institute of Neurology, University College London, UK.
Roshni
R
Desai
Department of Neuroinflammation, Institute of Neurology, University College London, UK.
Kenneth J
KJ
Smith
Clinical Pharmacology and Experimental Therapeutics, Division of Medicine, University College London, UK; UCL Centre for Cardiovascular and Metabolic Neuroscience University College London, Gower Street, London WC1E 6BT, UK. Electronic address: n.marina@ucl.ac.uk.
Nephtali
N
Marina
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism*; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology
Arterial hypertension; Astrogliosis; Hypoxia; Sympathetic nervous system