title: Sex and hormonal influences on the nicotine-induced attenuation of isoprenaline vasodilations in the perfused rat kidney.
abstract: We previously reported that nicotine impairs betta-adrenoceptor-mediated renovascular control in male rats. Here, we investigated the roles of sex and estrogen in nicotine-betta-adrenoceptor renal interaction. The effect of nicotine on renal vasodilations caused by isoprenaline was evaluated in phenylephrine-preconstricted perfused kidneys of male and proestrus female rats in absence and presence of NG-nitro-<span class="smallcap">l</span>-arginine (<span class="smallcap">l</span>-NNA, a NOS inhibitor). The interaction was also studied in diestrus and ovariectomized (OVX) rats treated with or without estradiol, tamoxifen, or <span class="smallcap">l</span>-arginine. Bolus isoprenaline (0.03-8.0 micromol) elicited dose-dependent renal vasodilations; female preparations were more sensitive (smaller ED50) to isoprenaline-induced vasodilation than were male preparations. Infusion of nicotine (500 micromol/L) reduced isoprenaline vasodilations in the 2 sexes and abolished male-female differences in isoprenaline responses. <span class="smallcap">l</span>-NNA reduced isoprenaline vasodilations in proestrus but not in male preparations. Also, in the presence of <span class="smallcap">l</span>-NNA, nicotine caused no attenuation of isoprenaline vasodilations in proestrus preparations. Renal responses to isoprenaline together with the attenuation of these responses by nicotine were reduced by OVX and restored to near-proestrus levels after supplementation with estradiol, the estrogen receptor modulator tamoxifen, or <span class="smallcap">l</span>-arginine. In diestrus rats, which exhibited reduced plasma estradiol, nicotine caused less attenuation of isoprenaline vasodilations. We conclude that impairment of estrogen-NOS signaling constitutes a possible cellular mechanism for the detrimental effect of nicotine on isoprenaline vasodilations in female rats. The mechanism of the nicotine-induced attenuation of isoprenaline vasodilation in male kidneys, which is NOS-independent, remains to be elucidated.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, 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
mesh_terms: D000818:Animals; D004967:Estrogens / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004967:Estrogens; D012739:Gonadal Steroid Hormones; D009538:Nicotine; D007545:Isoproterenol