Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 834, Issue -, Pages 36-44Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2018.07.008
Keywords
Nicotine; Endotoxemia; alpha 7-nAChRs; alpha 4 beta 2-nAChRs; Hypotension; Cardiac sympathovagal balance; Inflammation
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Funding
- Science and Technology Development Fund, Egypt (STDF) [14895]
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The cholinergic antiinflammatory pathway favorably influences end organ damage induced by inflammatory conditions. Here, we hypothesized that alpha 7 and/or alpha 4 beta 2-nicotinic acetylcholine receptors (nAChRs) protect against cardiovascular and autonomic imbalances induced by endotoxemia in rats. We assessed dose-effect relationships of i.v. nicotine (25, 50, or 100 mu g/kg), PHA-543613 (alpha 7-nAChR agonist; 0.2 or 2.0 mg/kg), or 5-iodoA- 85380 (5IA, alpha 4 beta 2-nAChRs agonist; 0.01 or 0.1 mg/kg) on cardiovascular and inflammatory responses elicited by lipopolysaccharide (LPS, 10 mg/kg i.v.). The two lower doses of nicotine caused dose-dependent attenuation of hypotensive and tachycardic responses of LPS. Nicotine also reversed LPS-evoked reductions in time-domain indices of heart rate variability (HRV) and spectral measure of cardiac sympathovagal balance. Alternatively, hypotensive and tachycardic effects of LPS were (i) partly and dose-dependently reversed after selective activation of alpha 7 (PHA) or alpha 4 beta 2-nAChRs (5IA), and (ii) completely eliminated after co-treatment with the smaller doses of the two agonists. Further, PHA or 5IA abolished the reducing effect of LPS on time and spectral measures of HRV. Elevations in serum tumor necrosis factor-alpha (TNF-alpha) observed in LPS-treated rats were compromised upon co-administration of nicotine, PHA, or 5IA. In conclusion, monomeric alpha 7 or heteromeric alpha 4 beta 2-nAChRs favorably and additively influence inflammatory and associated cardiovascular anomalies induced by endotoxemia.
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