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Enhancement of Hypothalamic Corticotrophin Releasing Hormone Signal Contributes to Elevated Sympathetic Outflow in Spontaneous Hypertension Rat
Author(s) -
Zhou JingJing,
Shao JianYing,
Ma HuiJie,
Pan HuiLin,
Li DePei
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.744.7
Subject(s) - medicine , endocrinology , corticotropin releasing hormone , hypothalamus , vasomotor , microinjection , blood pressure , antagonist , sympathetic nervous system , chemistry , receptor
The paraventricular nucleus (PVN) of the hypothalamus is crucially involved in the regulation of blood pressure and sympathetic outflow in hypertension. The PVN contains neurons synthesizing corticotrophin releasing hormone (CRH), a neuropeptide that is critical in regulating neuroendocrine and cardiovascular functions in physiological and disease conditions. The mRNA and protein expression levels are significantly increased in the hypothalamus in patients with primary hypertension. However, the role of hypothalamic CRH signal in the elevated sympathetic vasomotor tone in hypertension remains unknown. In this study, we tested a hypothesis that enhanced hypothalamic CRH signals contributes to elevated sympathetic vasomotor tone in primary hypertension. Western blotting analysis by using PVN tissues revealed that CRH receptor (CRHR) 1 expression level was significantly higher in male adult spontaneously hypertensive rats (SHRs) than in Wistar‐Kyoto (WKY) rats. However, CRHR1 expression level in the PVN was not significantly affected by lowing ABP by celiac ganglionectomy in SHRs. In brain slice preparation, bath application of CRH induced a significantly greater membrane depolarization and an increase in the firing rate of spinally projecting PVN neurons in SHRs than in WKY rats. A CRHR1 antagonist NBI 35965, not CRHR2 antagonist antisauvagine‐30, decreased the basal firing rate of spinally projecting PVN neurons in SHRs but not in WKY rats. However, CRH did not change neither the miniature inhibitory post‐synaptic currents nor the miniature excitatory post‐synaptic currents of labeled PVN neurons in both SHRs and WKY rats. Furthermore, bilateral microinjection of CRH into the PVN induced dose‐dependently greater increases in arterial blood pressure (ABP), heart rate (HR), and renal sympathetic activity (RSNA) in anesthetized SHRs than in WKY rats. CRH‐induced sympathoexcitatory effect was eliminated by microinjection of NBI 35965 but not antisauvagine‐30. Microinjection of NBI 35965 into the PVN significantly reduced basal ABP, HR, and RSNA in SHRs. These data suggest that upregulation of CRFR1 receptor in the PVN is involved in hyperactivity of spinally projecting PVN neurons and contributes to the elevated sympathetic outflow in essential hypertension. Support or Funding Information Supported by grants from National Institutes of Health (HL139523 and HL142133). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .