title: Nicotine paradoxically affects the facilitatory effect of ovarian hormones on the adenosine receptor-mediated renal vasodilation.
abstract: We tested the hypothesis that nitric oxide synthase (NOS) and/or heme oxygenase (HO) modulate the hormonally-dependent nicotine interaction with adenosine receptor-mediated renal vasodilations. Vasodilations caused by 5'-N-ethylcarboxamidoadenosine (NECA) in phenylephrine-preconstricted perfused kidneys were reduced in ovariectomized (OVX) rats and restored to sham levels after treatment with estrogen (E2), medroxyprogesterone acetate (MPA) or their combination. The facilitatory action of E2 or MPA was abolished after blockade of their respective receptors by ICI-182780 and mifepristone, or inhibition of NOS (N(ω)-nitro-L-arginine-methyl ester, L-NAME) but not HO (zinc protoporphyrin, ZnPP). NECA vasodilations were (i) decreased and increased by nicotine (1 mg/kg/day, 2 weeks) in OVX/MPA and OVX/E2 kidneys, respectively, and (ii) resistant to nicotine in females with deficient (OVX) or balanced (sham or E2/MPA-replaced OVX) hormonal milieu. The attenuation of NECA responses by nicotine in OVX/MPA kidneys disappeared after treatment with hemin (HO inducer) but not L-arginine (NOS substrate). Alternatively, nicotine enhancement of NECA responses in OVX/E2 kidneys was abolished following treatment with ICI 182780 or L-NAME. Overall, the NOS-coupled E2/progesterone receptor contributes to the enhancement of NECA vasodilations by ovarian hormones. Further, HO inhibition and NOS facilitation mediate the directionally opposite effects of nicotine on NECA responses in MPA- or E2-replaced OVX rats, respectively.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Eman Y
authors.initials: EY
authors.lastname: Gohar
authors.forename: Sahar M
authors.initials: SM
authors.lastname: El-gowilly
authors.forename: Hanan M
authors.initials: HM
authors.lastname: El-Gowelli
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
mesh_terms: D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D004967:Estrogens / Q000097:blood / Q000494:pharmacology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D011374:Progesterone; D009538:Nicotine; D017258:Medroxyprogesterone Acetate; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)