Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats.
We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1-16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE₂) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(SNP)). Nicotine (100 μg/kg i.v.) reduced BRS(SNP) in OVX rats but not in proestrus or OVXE₂ rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS(PE) was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine-BRS(SNP) interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS(SNP) attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E₂ against nicotine-induced baroreceptor dysfunction in female rats.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. mahelm@hotmail.com
Mahmoud M
MM
El-Mas
Mohamed A
MA
Fouda
Sahar M
SM
El-Gowilly
Evan I
EI
Saad
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010052:Ovariectomy; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*; D012737:Sex Factors; D013610:Tachycardia / Q000503:physiopathology*
D004967:Estrogens; D018722:Nicotinic Agonists; D011960:Receptors, Estrogen; D009599:Nitroprusside; D010656:Phenylephrine; D000077267:Fulvestrant; D004958:Estradiol; D009538:Nicotine