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The role of Corticotrophin Releasing Hormone in Paraventricular Nucleus in Elevated Sympathetic Outflow in Spontaneous Hypertension Rat
Author(s) -
Zhou Jingjing,
Ma HuiJie,
Li DePei
Publication year - 2018
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.2018.32.1_supplement.918.5
Subject(s) - microinjection , medicine , endocrinology , corticotropin releasing hormone , hypothalamus , antagonist , basal (medicine) , receptor , blood pressure , nucleus , sympathetic nervous system , chemistry , insulin , psychiatry
Corticotrophin releasing hormone (CRH) is one of the critical neuropeptides that regulate neuroendocrine and autonomic function. CRH expression level is significantly increased in the hypothalamic in patients with essential hypertension. However, the roles of CRH in the regulation of blood pressure and sympathetic outflow is unknown. We hypothesized that CRH and its receptors in the paraventricular nucleus (PVN) in the hypothalamus are involved elevated sympathetic vasomotor tone in essential hypertension. Arterial blood pressure basal (ABP), heart rate (HR), and renal sympathetic activity (RSNA) were recorded in anesthetized male adult spontaneous hypertension rats (SHR) and its normotensive control Wistar‐Kyoto (WKY) rats. Bilateral microinjection of CRH into the PVN dose‐dependently increased the ABP, HR, and RSNA in both SHRs and WKY rats. CRH‐induced sympathoexcitatory effect was significantly greater in SHR than in WKY rats and this effect was eliminated by microinjection of the CRH receptor 1 (CRHR1) specific antagonist NBI 35965 but not antisauvagine‐30, the specific antagonist for CRH receptor 2 (CRHR2). Bilateral microinjection of NBI 35965 into PVN significantly reduced the basal ABP, HR, and RSNA in SHR but in WKY rats. However, microinjection the antagonist antisauvagine‐30 into the PVN did not significantly alter ABP, HR, and RSNA in either SHR or WKY rats. Furthermore, the CRHR1 immunoreactivity was positive in retrogradely labeled PVN‐RVLM neurons. In addition, western blotting analysis revealed that CRHR1 expression levels in the PVN was significantly higher in SHR than in WKY rats. These data suggest that the enhanced CRH and its receptor function in the PVN is involved in elevated sympathetic drive in essential hypertension. Support or Funding Information This work was supported by the National Institutes of Health (Grants MH096086 to D.‐P. L.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .