الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
1.A single challenge with LPS for 6 hrscaused significant reductions in SBP, renal pressor responses to phenylephrine and vasopressinand vasodilatory responses to NECA, but not ACh, along with elevations in serum IL-1β,urea and creatinine and renalNFκB/iNOS/HO-1expression. These LPS effects were sex unrelated since they were demonstrated in rats of both sexes,except for hypotension and elevation of renal NFκB/iNOS expression which were more evident in male population. Apart from the LPS hypotension in male rats, these parameters were restored to near-control levels 1 day after the septic insult.
2.After 2 days of LPS administration (i) serum markers of renal function and renal NFκB/iNOS expression remained unchanged in the two rat sexes, and (ii) falls in SBP, enhancement of ACh and NECA renal vasodilations and elevation of renal NFκB/iNOS expression were observed irrespective of the rat sex. None of the above hemodynamic or renal parameters were different from control values when measured 6 days after the endotoxic insult in both male and female rats. Alternatively, the rat mortality was progressively increased over the 6-day of the study, with this effect being more significantly apparent in male compared with female rats. Thedata suggest the duration of LPS exposure, rat sex, and specific biologic activity are important determinant of the magnitude and direction of the biological effects of endotoxemia.
3.The 6-hr LPS responses, except HO-1 upregulation, were alleviated after co-treatment with nicotine,andthesefavorable nicotine actionsdissipated after α7-nicotinic receptor blockade (MLA) or HO-1inhibition (ZnPP).Moreover, the inflammation and renal vasoconstrictor hyporeactivity elicited by LPS were
SUMMARY AND CONCLUSIONS110reversed byhemin or CORM-2 treatment while the mortality and alterations in renal function biomarkers and vasodilator responses were abrogated by bilirubin. 4.The data obtained from 6-hr study underscorethe valuable roles of α7-nicotinic receptors and HO-1pathwayin modulating nicotine/LPSinteraction. The activation of α7-nicotinic receptors and subsequent upregulation of HO-1/carbon monoxide/bilirubinpathway constitute critical steps in nicotine counteraction of lethal, inflammatory and renal consequences of acute endotoxemia. 5.The 2-dayLPS treatment lowered BP, enhanced renal vasodilatory responses to ACh and NECA, and caused opposite changes in renal expression of HSP70 (decreases) and α7-nAChRs/α4β2-nAChRs/iNOS (increases). Such responses, except hypotension,were largely eliminated after co-exposure to nicotine, pentoxifylline (TNFα inhibitor), or aminoguanidine (iNOS inhibitor). Moreover, the counteraction by nicotine of the facilitatory action of LPS on the renal vasodilator capacity disappeared after selective blockade of α7-nAChRs (MLA) or α4β2-nAChRs (DHβE) or inhibition of HSP70 (quercetin).6.Pharmacologic and immunohistochemical results of 2-day study revealed a crosstalk betweenα7/α4β2nAChRs and HSP70 in modulating the advantageous counteractive effects of nicotine on inflammatory and renovascular consequencesof 2-day endotoxemia.7.Clinically, the data advocate potential therapeutic relevancefor nicotine or perhaps selective α7orα4β2nAChRsagonistsin the control ofalteredrenal hemodynamics andvascularreactivityobserved in endotoxic patients. Whilst the therapeutic application of nicotine is still restricted dueto its lack of specificity, thisstudy may provide basis for potential specific therapeutic targets for management of inflammation,renal dysfunction and vascular refractoriness to vasoconstrictors and vasodilatorsobserved during endotoxemia.