Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Toxicol Appl Pharmacol. 2012 Feb 1;258(3):410-7. doi: 10.1016/j.taap.2011.12.011. Epub 2011 Dec 19.
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.
我们之前的研究表明，与对反射性心动过缓没有影响相比，急性暴露于尼古丁会优先减弱雄性大鼠的压力感受器介导的反射性心动过速的控制。在这里，我们研究了雌性大鼠是否像雄性大鼠一样对尼古丁的降压反射作用敏感，以及这种相互作用是否受到雌激素的调节。在清醒自由活动的发情前期、卵巢切除（OVX）和雌激素（50μg/kg/天皮下注射，5 天）替代 OVX（OVXE₂）大鼠中，构建了静脉内给予（1-16μg/kg）去氧肾上腺素（PE）或硝普钠（SNP）引起的反射性变时反应的反射性心动过速曲线。曲线的斜率被用作反射敏感性（BRS（PE）和 BRS（SNP））的测量值。尼古丁（100μg/kg 静脉内注射）降低了 OVX 大鼠的 BRS（SNP），但对发情前期或 OVXE₂大鼠没有影响。在发情后期大鼠中，尼古丁对反射性心动过速的抑制作用也很明显，其血浆雌激素水平与 OVX 大鼠相似。在所有大鼠制剂中，尼古丁均不影响 BRS（PE）。然后进行了实验以确定中枢雌激素受体是否调节尼古丁-BRS（SNP）相互作用。OVX 大鼠给予硫酸雌二醇（0.2μg/大鼠）颅内治疗，消除了静脉内尼古丁对 BRS（SNP）的减弱作用。当 OVX 大鼠预先用颅内 ICI 182,780（50μg/大鼠，选择性雌激素受体拮抗剂）预处理时，雌激素的这种保护作用消失。这些发现表明，中枢雌激素受体神经元池是 E₂对雌性大鼠尼古丁引起的压力感受器功能障碍提供保护的基础。
