Estrogen dependence of the renal vasodilatory effect of nicotine in rats: Role of α7 nicotinic cholinergic receptor/eNOS signaling

Academic Article


  • Aims: 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. Main methods: Nicotine-evoked vasodilation was evaluated in phenylephrine-preconstricted perfused kidneys obtained from male, proestrus female, ovariectomized (OVX) and estrogen-replaced OVX (OVXE2) rats. Key findings: 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 NG-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 E2 in OVX rats. The nitrite/nitrate levels and protein expressions of eNOS and α7 nicotinic cholinergic receptor (α7 nAChRs) were significantly higher in renal tissues of OVXE2 compared with OVX rats, suggesting a facilitatory effect for E2 on α7 nAChRs/eNOS signaling. Significance: 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 α7 nAChRs in this estrogen-dependent phenomenon. © 2010 Elsevier Inc. All rights reserved.
  • Authors

    Published In

  • Life Sciences  Journal
  • Digital Object Identifier (doi)

    Author List

  • El-Mas MM; El-Gowilly SM; Gohar EY; Ghazal ARM; Abdel-Rahman AA
  • Start Page

  • 187
  • End Page

  • 193
  • Volume

  • 88
  • Issue

  • 3-4