RT Journal Article
SR Electronic
T1 Estrogen Provokes the Depressant Effect of Chronic Nicotine on Vagally Mediated Reflex Chronotropism in Female Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 568
OP 575
DO 10.1124/jpet.112.191940
VO 342
IS 2
A1 Mahmoud M. El-Mas
A1 Hanan M. El-Gowelli
A1 Sahar M. El-Gowilly
A1 Mohamed A. Fouda
A1 Mai M. Helmy
YR 2012
UL http://jpet.aspetjournals.org/content/342/2/568.abstract
AB 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 (OVXE2) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRSPE and BRSSNP). 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 BRSPE but not BRSSNP 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.