Tseng C J, Appalsamy M, Robertson D, Mosqueda-Garcia R
Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee.
J Pharmacol Exp Ther. 1993 Jun;265(3):1511-8.
The role of the central nervous system in the pressor effect of nicotine is not well understood. In this study, we evaluated the cardiovascular effects of nicotine in the lower brainstem of normotensive and hypertensive rats. Microinjection of nicotine (0.012-3696 pmol/60 nl) into the nucleus of the solitary tract and area postrema of Sprague-Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) decreased blood pressure and heart rate. In contrast, administration of similar doses of nicotine within the rostral ventrolateral medulla (RVLM) evoked a long-lasting pressor and tachycardic effect. This pressor effect was completely abolished by prior microinjection of hexamethonium. In SHR the depressor and bradycardic responses in the nucleus of the solitary tract and area postrema were similar to those of normotensive animals. The pressor effect in the RVLM, however, was more pronounced in the SHR than in WKY or SD rats. In additional experiments, the changes produced by intra-RVLM administration of nicotine on renal sympathetic nerve activity, blood pressure and heart rate were evaluated before and after equidepressor intravenous doses of either clonidine, labetalol or prazosin. The prior administration of labetalol antagonized the pressor effect of nicotine in the three strains of rats (SHR, 82 +/- 6%; SD, 96 +/- 4%; WKY, 83 +/- 9%). Prazosin inhibited the nicotine pressor response by 69% in SHR, by 44% in SD and by 70% in WKY. Clonidine had no effect on nicotine response in the three groups of rats. In conclusion, nicotine administration within the RVLM increases renal sympathetic nerve activity and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
中枢神经系统在尼古丁升压效应中的作用尚未完全明确。在本研究中,我们评估了尼古丁对正常血压和高血压大鼠延髓下部的心血管效应。向Sprague-Dawley(SD)、Wistar Kyoto(WKY)和自发性高血压大鼠(SHR)的孤束核和最后区微量注射尼古丁(0.012 - 3696 pmol/60 nl)可降低血压和心率。相反,在延髓头端腹外侧区(RVLM)注射相似剂量的尼古丁会引发持久的升压和心动过速效应。预先微量注射六甲铵可完全消除这种升压效应。在SHR中,孤束核和最后区的降压和心动过缓反应与正常血压动物相似。然而,RVLM中的升压效应在SHR中比在WKY或SD大鼠中更明显。在额外的实验中,在静脉注射等效降压剂量的可乐定、拉贝洛尔或哌唑嗪前后,评估了RVLM内注射尼古丁对肾交感神经活动、血压和心率的影响。预先给予拉贝洛尔可拮抗尼古丁在三种品系大鼠(SHR,82±6%;SD,96±4%;WKY,83±9%)中的升压效应。哌唑嗪在SHR中抑制尼古丁升压反应69%,在SD中抑制44%,在WKY中抑制70%。可乐定对三组大鼠的尼古丁反应均无影响。总之,在RVLM内给予尼古丁会增加肾交感神经活动和血压。(摘要截取自250字)