title: Estrogen provokes the depressant effect of chronic nicotine on vagally mediated reflex chronotropism in female rats.
abstract: We recently reported that acute nicotine impairs reflex tachycardic activity in estrogen-depleted, but not estrogen-repleted, female rats, suggesting a restraining influence for estrogen against the nicotine effect. In this study, we tested whether the baroreflex-protective effect of estrogen can be replicated when nicotine was administered chronically. We also report on the dose dependence and autonomic modulation of the nicotine-baroreflex interaction. The effects of nicotine (0.5, 1, or 2 mg/kg/day for 14 days) on baroreflex curves relating changes in heart rate to increases [phenylephrine (PE)] or decreases [sodium nitroprusside (SNP)] in blood pressure were evaluated in sham-operated (SO), ovariectomized (OVX), and estrogen-replaced OVX (OVXE(2)) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)). In SO rats, both reflex bradycardic and tachycardic responses were attenuated by nicotine in a dose-related fashion. In nicotine-treated rats, blockade of β-adrenergic (propranolol), but not muscarinic (atropine), receptors caused additional reductions in reflex chronotropic responses, implying that nicotine selectively impairs reflex vagal activity. OVX selectively decreased BRS(PE) but not BRS(SNP) and abolished the nicotine-induced impairment of either response. These effects of OVX were reversed after treatment with estrogen or the estrogen receptor modulator raloxifene. In atropine-treated rats, comparable BRS values were demonstrated in all rat preparations regardless of the estrogen or nicotine milieu. Collectively, the inhibition of vagal activity accounts for the depressant effect of chronic nicotine on baroreflex activity. Furthermore, contrary to nicotine's acute effects, the baroreflex-attenuating effect of chronic nicotine is exacerbated by estrogen.
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: Hanan M
authors.initials: HM
authors.lastname: El-Gowelli
authors.forename: Sahar M
authors.initials: SM
authors.lastname: El-Gowilly
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Fouda
authors.forename: Mai M
authors.initials: MM
authors.lastname: Helmy
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013610:Tachycardia / Q000188:drug therapy / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D004967:Estrogens; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D010656:Phenylephrine; D020849:Raloxifene Hydrochloride; D009538:Nicotine; D011433:Propranolol