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Inconsistent effects of surgical and chemical castration on arterial baroreceptor dysfunction and cardiac and brainstem inflammation in endotoxic rats
Author(s) -
Sallam Marwa Y.,
El-Gowilly Sahar M.,
El-Mas Mahmoud M.
Publication year - 2020
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.2020.34.s1.02689
Subject(s) - baroreflex , phenylephrine , endocrinology , medicine , baroreceptor , rostral ventrolateral medulla , blood pressure , mean arterial pressure , heart rate
Impaired cardiac autonomic and arterial baroreflex activity has been implicated in cardiovascular derangements induced by endotoxemia. In this communication, we tested the hypothesis that androgenic hormones contribute to endotoxic manifestations of arterial baroreflex dysfunction and related cardiac and central neuroinflammatory pathways in male rats. Baroreflex curves relating changes in heart rate to increases or decreases in blood pressure evoked by phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious sham‐operated and castrated rats treated with or without lipopolysaccharide (LPS, 10 mg/kg i.v.). Slopes of baroreflex curves were used as measures of baroreflex sensitivity (BRS). In sham rats, LPS caused significant reductions in BRS and increases in the immunohistochemical expression of NFκB in cardiac tissues as well as in brainstem neurons of the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM). The baroreflex depressant effect of LPS was maintained in CAS rats despite significant attenuation of the inflammatory response in cardiac and brainstem areas. We also evaluated the effects of pharmacologic inhibition of androgenic biosynthetic pathways on LPS responses. Whereas none of the LPS effects were altered after prior exposure to formestane (aromatase inhibitor, 15 mg/kg s.c)‐pretreated rats, the LPS‐evoked BRS PE , but not BRS SNP , depression and cardiac and neuronal inflammation disappeared in intact rats pretreated with degarelix (gonadotropin‐releasing hormone receptor blocker, 1 mg/kg s.c.). On the other hand, the prior inhibition of 5α‐reductase by finasteride (20 mg/kg s.c) did not affect baroreflex dysfunction induced by LPS and reduced cardiac, but not neuronal, NFκB expression. The data highlight advantageous effects for the inhibition of hypothalamic‐pituitary‐gonadal axis in counteracting baroreflex dysfunction caused by endotoxemia and predisposing cardiac and neuroinflammatory signals. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)