Home
Resources
Publications
Brainstem Cholinergic Pathways Diminish Cardiovascular and Neuroinflammatory Actions of Endotoxemia in Rats: Role of NFκB/α7/α4β2AChRs Signaling

Brainstem Cholinergic Pathways Diminish Cardiovascular and Neuroinflammatory Actions of Endotoxemia in Rats: Role of NFκB/α7/α4β2AChRs Signaling

Marwa Y Sallam, Sahar M El-Gowilly, Mohamed A Fouda, Mohammed M Abd-Alhaseeb, Mahmoud M El-Mas

Neuropharmacology. 2019 Oct;157:107683.

PMID: 31247270

Abstract:

Nicotine improves endotoxic manifestations of hypotension and cardiac autonomic dysfunction in rats. Here, we test the hypothesis that brainstem antiinflammatory pathways of α7/α4β2 nicotinic acetylcholine receptors (nAChRs) modulate endotoxic cardiovascular derangements. Pharmacologic and molecular studies were performed to determine the influence of nicotine or selective α7/α4β2-nAChR ligands on cardiovascular derangements and brainstem neuroinflammation caused by endotoxemia in conscious rats. The i.v. administration of nicotine (50 μg/kg) abolished the lipopolysaccharide (LPS, 10 mg/kg i.v.)-evoked: (i) falls in blood pressure and spectral measure of cardiac sympathovagal balance (ratio of the low-frequency to high-frequency power, LF/HF), (ii) elevations in immunohistochemical protein expressions of NFκB and α4β2-nAChR in medullary neurons of the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), and (iii) decreases in medullary α7-nAChR protein expression. These favorable nicotine influences were replicated in rats treated intracisternally (i.c.) with PHA-543613 (selective α7-nAChR agonist) or 5-iodo-A-85380 (5IA, selective α4β2-nAChRs agonist). Measurement of arterial baroreflex activity by the vasoactive method revealed that nicotine, PHA, or 5IA reversed the LPS depression of reflex bradycardic, but not tachycardic, activity. Moreover, the counteraction by nicotine of LPS hypotension was mostly inhibited after treatment with i.c. methyllycaconitine (MLA, α7-nAChR antagonist) in contrast to a smaller effect for dihydro-β-erythroidine (DHβE, α4β2-nAChR antagonist), whereas the associated increases in LF/HF ratio remained unaltered. The data signifies the importance of brainstem α7, and to a lesser extent α4β2, receptors in the nicotine counteraction of detrimental cardiovascular and neuroinflammatory consequences of endotoxemia.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP213550824	5-Iodo-A-85380 dihydrochloride hydrate		213550-82-4 (free base)	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: