Additive counteraction by α7 and α4β2-nAChRs of the hypotension and cardiac sympathovagal imbalance evoked by endotoxemia in male rats

European Journal of Pharmacology
Marwa Y SallamMahmoud M El-Mas

Abstract

The cholinergic antiinflammatory pathway favorably influences end organ damage induced by inflammatory conditions. Here, we hypothesized that α7 and/or α4β2-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 μg/kg), PHA-543613 (α7-nAChR agonist; 0.2 or 2.0 mg/kg), or 5-iodo-A-85380 (5IA, α4β2-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 α7 (PHA) or α4β2-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-α (...Continue Reading

Citations

Jan 4, 2020·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Abdalla M WednMahmoud M El-Mas
Jul 12, 2019·Frontiers in Physiology·Fernanda BrognaraHelio Cesar Salgado
May 28, 2021·Clinical and Experimental Pharmacology & Physiology·Shrouk S ElzokmMahmoud M El-Mas
Jul 30, 2021·Biochemical Pharmacology·Abdalla M WednMahmoud M El-Mas
Sep 2, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Yasser H HabibMahmoud M El-Mas

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