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Gonadal Hormone Receptors Underlie The Resistance Of Female Rats To Cardiovascular Complications Of Endotoxemia
Author(s) -
ElLakany Mohammed A,
ElGowelli Hanan M,
Fouda Mohamed A,
ElGowilly Sahar M,
ElMas Mahmoud M
Publication year - 2017
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.31.1_supplement.848.4
Subject(s) - medicine , endocrinology , estrogen , estrogen receptor , receptor , heart rate , blood pressure , hormone , cancer , breast cancer
Gender differences exist in the immunological and cardiovascular complications of sepsis, with the male gender being more vulnerable to these conditions. The current study tested the hypotheses that female rats are protected against the endotoxemia‐evoked hypotension and cardiac autonomic dysfunction, and that the presence of functional gonadal hormone receptors is a prerequisite for such protection. Changes in blood pressure (BP), heart rate (HR) and cardiac sympathovagal balance, as indexed by the analysis of heart rate variability (HRV), caused by a single i.v. dose of lipopolysaccharide (LPS, 10 mg/kg) were determined in conscious male and female rats. In male rats, LPS caused significant falls in BP and increases in HR. The spectral index of the cardiac sympathovagal balance (low‐frequency/high‐frequency ratio (LF/HF) of interbeat intervals was reduced by LPS, suggesting a shift in cardiac autonomic control towards parasympathetic dominance. Remarkably, none of the above cardiovascular effects of LPS was evident in female rats. We also report that pretreatment of female rats with fulvestrant (nonselective estrogen receptor blocker), PHTPP (estrogen receptor‐β blocker), mifepristone (progesterone receptor blocker) or formestane (aromatase inhibitor) uncovered clear hypotensive and tachycardic responses to LPS. Moreover, these female rats, unlike their male counterparts, exhibited increases, rather than decreases, in LF/HF ratio in response to LPS. Alternatively, LPS failed to modify the cardiovascular function in female rats pretreated with MPP, a selective blocker of estrogen receptor‐α. These findings highlight important roles for estrogen receptor‐β and progesterone receptors in guarding against cardiovascular derangements caused by endotoxemia in female rats. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)