title: Estrogen dependence of the renal vasodilatory effect of nicotine in rats: role of α7 nicotinic cholinergic receptor/eNOS signaling.
abstract: OBJECTIVE
  We recently reported that acute exposure to nicotine vasodilates the renal vasculature of male rats via facilitation of endothelial nitric oxide synthase (eNOS). In this study, we investigated whether this effect of nicotine is sexually dimorphic and the role of estrogen in modulating the nicotine effect.
  
  
  METHODS
  Nicotine-evoked vasodilation was evaluated in phenylephrine-preconstricted perfused kidneys obtained from male, proestrus female, ovariectomized (OVX) and estrogen-replaced OVX (OVXE(2)) rats.
  
  
  RESULTS
  Nicotine infusion (5×10(-5), 1×10(-4), and 5×10(-4) M) produced greater concentration-dependent reductions in the renal perfusion pressure (RPP) in an isolated kidney from proestrus females than from males. Inhibition of NOS by N(G)-nitro-L-arginine abolished the nicotine-evoked reduction in RPP and abolished the gender difference in the nicotine effect. Nicotine vasodilation was also attenuated in kidneys isolated from OVX and diestrus rats, models characterized by reduced estrogen levels. Further, estrogen or L-arginine supplementation in OVX rats largely restored the renal vasodilatory response to nicotine. Estrogen receptor blockade by tamoxifen abrogated the enhanced nicotine-evoked vasodilation elicited by E(2) in OVX rats. The nitrite/nitrate levels and protein expressions of eNOS and α(7) nicotinic cholinergic receptor (α(7) nAChRs) were significantly higher in renal tissues of OVXE(2) compared with OVX rats, suggesting a facilitatory effect for E(2) on α(7) nAChRs/eNOS signaling.
  
  
  CONCLUSIONS
  Estrogen-dependent facilitation of NOS signaling mediates the enhanced vasodilator capacity of nicotine in the renal vasculature of female rats. Preliminary evidence also suggests a potential role for α(7) nAChRs in this estrogen-dependent phenomenon.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. mahelm@hotmail.com
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: el-Mas
authors.forename: Sahar M
authors.initials: SM
authors.lastname: el-Gowilly
authors.forename: Eman Y
authors.initials: EY
authors.lastname: Gohar
authors.forename: Abdel-Rheem M
authors.initials: AR
authors.lastname: Ghazal
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D015153:Blotting, Western; D004958:Estradiol / Q000097:blood / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D004958:Estradiol; D009538:Nicotine; D052250:Nitric Oxide Synthase Type III