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Hypothalamic Corticotrophin‐Releasing Factor and Norepinephrine Mediate Sympathetic and Cardiovascular Responses to Acute Intracarotid Injection of Tumour Necrosis Factor‐α in the Rat
Author(s) -
Zhang Z.H.,
Felder R. B.
Publication year - 2008
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2008.01750.x
Subject(s) - medicine , endocrinology , norepinephrine , tumor necrosis factor alpha , tumor necrosis factor α , dopamine
Systemic administration of tumour necrosis factor (TNF)‐α induces the release of norepinephrine in the paraventricular nucleus (PVN) of hypothalamus and an increase in expression of corticotrophin‐releasing factor (CRF) and CRF type 1 receptors. We explored the hypothesis that CRF and norepinephrine in PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF‐α. In anaesthetised rats, the increases in arterial pressure and heart rate induced by intracarotid artery injection of TNF‐α were attenuated by intracerebroventricular (ICV) injection of either the α 1 ‐adrenergic antagonist prazosin or the CRF antagonist α‐helical CRF. Prazosin blocked the TNF‐α‐induced increase in renal sympathetic nerve activity (RSNA), whereas α‐helical CRF substantially reduced the RSNA response. Conversely, CRF and the α 1 ‐adrenergic agonist phenylephrine, administered ICV, both elicited increases in PVN neuronal activity, RSNA, arterial pressure and heart rate. Microinjection of CRF and phenylephrine directly into PVN evoked smaller responses. These results are consistent with the hypothesis that norepinephrine and CRF in the PVN mediate the cardiovascular and sympathetic responses to acute systemic administration of TNF‐α.