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The α7/α4β2 nAChRs Alleviate The Hypotension And Altered Cardiac Sympathovagal Balance Evoked By Endotoxemia In Male Rats
Author(s) -
Sallam Marwa Y,
ElGowilly Sahar M,
ElGowelli Hanan 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.848.3
Subject(s) - nicotine , agonist , cholinergic , pharmacology , nicotinic agonist , medicine , endocrinology , lipopolysaccharide , chemistry , receptor
Nicotine favorably influences inflammatory conditions such as endotoxemia and ulcerative colitis through the activation of the cholinergic antiinflammatory pathway. In this communication, we hypothesized that α7 and/or α4β2 nicotinic acetylcholine receptors (nAChRs) protect against the cardiovascular and autonomic imbalances caused by endotoxemia. Experiments were performed in conscious male rats to assess the dose‐effect relationships for i.v. nicotine (25, 50, or 100 μg/kg), PHA‐543613 (selective α7 nAChR agonist; 0.2 or 2.0 mg/kg), or 5‐iodo‐A‐85380 (5IA, selective α4β2 nAChRs agonist; 0.01 or 0.1 mg/kg) on cardiovascular responses elicited by lipopolysaccharide (LPS, 10 mg/kg i.v.). The two lower doses of nicotine (25 and 50 mg/kg) caused significant and dose‐dependent attenuation of the hypotensive and tachycardic responses caused by prior LPS administration. The effects of the 100 mg/kg dose of nicotine were comparable to those caused by the 25 mg/kg dose. The reductions in the time‐ domain indices of heart rate variability (HRV) and spectral measure of cardiac sympathovagal balance (ratio of the low‐frequency to high‐frequency power) induced by LPS were similarly reversed by nicotine. Alternatively, the hypotensive and tachycardic effects of LPS were (i) partly and dose‐dependently reversed after selective activation of α7 or α4β2 nAChRs by PHA or 5IA, respectively, and (ii) completely eliminated after treatment with a mixture of the smaller doses of the two agonists. By contrast, the individual or combined use of PHA or 5IA fully abolished the LPS‐evoked reductions in the low‐frequency/high‐frequency ratio, indicating the normalization of the cardiac sympathovagal balance. Together, the data implicate monomeric (α7) and heteromeric (α4β2) nAChRs in the nicotine counteraction of the adverse cardiovascular effects of endotoxemia. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895).