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Sex‐Unrelated Counteraction by Nicotine of the Endotoxemia‐Evoked Facilitation of Renal Vasodilator Capacity in Rats: Roles of α7/α4β2 nAChRs and HSP70
Author(s) -
Wedn Abdalla M.,
ElGowilly Sahar M.,
ElMas Mahmoud M.
Publication year - 2018
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.2018.32.1_supplement.562.8
Subject(s) - methyllycaconitine , nicotine , endocrinology , medicine , mecamylamine , vasodilation , pharmacology , kidney , chemistry , nicotinic agonist , nicotinic acetylcholine receptor , receptor
Nicotine has been shown to alleviate renal inflammation and injury induced by endotoxemia. The current study investigated (i) the sex specificity of the nicotine modulation of hemodynamic and renal vasodilatory responses to endotoxemia in rats, and (ii) the roles of α7 or α4β2 nAChRs and related HSP70/TNFα/iNOS signaling in the interaction. Endotoxemia was induced by i.p. administration of lipopolysaccharide (LPS, 5 mg/kg/day.) for 2 consecutive days and changes in systolic blood pressure (SBP, tail‐cuff plethysmography) and vasodilator responsiveness of isolated perfused kidney to acetylcholine (ACh) or 5′‐ N ‐ethylcarboxamidoadenosine (NECA, adenosine receptor agonist) were evaluated. Compared with saline values, LPS decreased SBP and increased renal vasodilations induced by cumulative bolus injections of ACh (0.01–7.29 nmol) or NECA (1.6–100 nmol). No changes in serum creatinine or urea were observed. These effects were not sexually differentiated as they were similarly observed in the two rat genders. The LPS facilitation of renal vasodilations were attenuated after concurrent administration of aminoguanidine (iNOS inhibitor, 50 mg/kg), pentoxifylline (TNFα inhibitor, 3 mg/kg), or nicotine (0.5, 1, or 2 mg/kg). We also report that the selective blockade of α7‐nAChRs (methyllycaconitine citrate, MLA) or α4β2‐nAChRs (dihydro‐β‐erythroidine, DHβE) (i) potentiated the enhancing action of LPS on ACh or NECA vasodilations, and (ii) abolished the depressant effect of nicotine on LPS facilitation of renal vasodilatory capacity. A similar inhibition of the nicotine effect was seen after inhibition of HSP70 by quercetin. Alternatively, LPS hypotension was eliminated in rats treated with the DHβE/nicotine or quercetin/nicotine regimen in contrast to no effect for nicotine alone or combined with MLA. These findings establish that nicotine offsets the LPS facilitation of the renal vasodilator propensity, an effect that is sex independent and possibly involves a crosstalk between HSP70 and nAChRs of the α7 and α4β2 types. Support or Funding Information Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .