title: PI3K/Akt-independent NOS/HO activation accounts for the facilitatory effect of nicotine on acetylcholine renal vasodilations: modulation by ovarian hormones.
abstract: We investigated the effect of chronic nicotine on cholinergically-mediated renal vasodilations in female rats and its modulation by the nitric oxide synthase (NOS)/heme oxygenase (HO) pathways. Dose-vasodilatory response curves of acetylcholine (0.01-2.43 nmol) were established in isolated phenylephrine-preconstricted perfused kidneys obtained from rats treated with or without nicotine (0.5-4.0 mg/kg/day, 2 weeks). Acetylcholine vasodilations were potentiated by low nicotine doses (0.5 and 1 mg/kg/day) in contrast to no effect for higher doses (2 and 4 mg/kg/day). The facilitatory effect of nicotine was acetylcholine specific because it was not observed with other vasodilators such as 5'-N-ethylcarboxamidoadenosine (NECA, adenosine receptor agonist) or papaverine. Increases in NOS and HO-1 activities appear to mediate the nicotine-evoked enhancement of acetylcholine vasodilation because the latter was compromised after pharmacologic inhibition of NOS (L-NAME) or HO-1 (zinc protoporphyrin, ZnPP). The renal protein expression of phosphorylated Akt was not affected by nicotine. We also show that the presence of the two ovarian hormones is necessary for the nicotine augmentation of acetylcholine vasodilations to manifest because nicotine facilitation was lost in kidneys of ovariectomized (OVX) and restored after combined, but not individual, supplementation with medroxyprogesterone acetate (MPA) and estrogen (E2). Together, the data suggests that chronic nicotine potentiates acetylcholine renal vasodilation in female rats via, at least partly, Akt-independent HO-1 upregulation. The facilitatory effect of nicotine is dose dependent and requires the presence of the two ovarian hormones.
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.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Sahar M
authors.initials: SM
authors.lastname: El-gowilly
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Hanan M
authors.initials: HM
authors.lastname: El-Gowelli
authors.affiliation: Medical Biotechnology Department, City for Scientific Research & Technology Applications, Borg El-Arab, Alexandria, Egypt.
authors.forename: Maha A
authors.initials: MA
authors.lastname: El-Demellawy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D001120:Arginine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010208:Papaverine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D006728:Hormones; D010656:Phenylephrine; D015735:Mifepristone; D019830:Adenosine-5'-(N-ethylcarboxamide); D004958:Estradiol; D009538:Nicotine; D006427:Hemin; D001120:Arginine; D017258:Medroxyprogesterone Acetate; D010208:Papaverine; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine
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