Tankersley Clarke G, Bierman Alexis, Rabold Richard
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Inhal Toxicol. 2007 Jun;19(8):621-9. doi: 10.1080/08958370701353049.
Altered autonomic control of heart rate (HR) rhythm during exposure to particulate matter (PM) has been suggested in human and animal studies. Our lab has shown strain variation in HR regulation between quiescent C3H/HeJ (C3) and C57BL/6J (B6) mice: that is, C3 mice show a consistently higher HR by approximately 80 bpm compared with B6 mice during a normal 24-h circadian cycle. In the current study, we hypothesize that the balance between sympathetic and parasympathetic control of HR during PM exposure varies between C3 and B6 mice. Radiotelemeters were implanted in C3 and B6 mice to measure HR responses and HR variability (HRV) parameters during successive 3-h exposures to filtered air (FA) or carbon black (CB, < 300 mug/m3). Exposures were repeated following administration of saline or parasympathetic (PS; atropine, 0.5 mg/kg i.p.) and sympathetic (S; propranolol, 1 mg/kg i.p.) blockade to study the autonomic regulation of HR during CB exposure. During FA exposure with saline, a significantly (p < .05) greater 3-h average HR response (bpm +/- SEM) occurred in C3 compared with B6 mice (496 +/- 22 vs. 427 +/- 3). With PS blockade, the strain difference between C3 and B6 mice was not evident (485 +/- 23 vs. 503 +/- 61). With S blockade, the 3-h average HR responses for C3 mice were significantly (p < .05) reduced compared with saline (413 +/- 18 vs. 392 +/- 15 for B6). During CB exposure with saline, HR responses were again significantly (p < 0.05) elevated in C3 compared with B6 mice, but these HR responses were not different relative to FA exposure. With S blockade, HR was significantly (p < .05) elevated in B6 mice during CB relative to FA, but was unchanged in C3 mice. Collectively, these results suggest that strain variation in HR regulation is due to a robust PS tone evident in B6 mice and a predominant S tone in C3 mice. Furthermore, CB exposure alters HR regulation in B6 mice by modulating a withdrawal of PS tone. Finally, strain variation in HR between B6 and C3 mice in responding to acute PM exposure implies that robust genetic determinants modulate altered autonomic regulation in susceptible individuals.
人体和动物研究表明,接触颗粒物(PM)期间心率(HR)节律的自主控制会发生改变。我们实验室已表明,在静息状态下,C3H/HeJ(C3)小鼠和C57BL/6J(B6)小鼠在心率调节方面存在品系差异:即在正常的24小时昼夜节律周期中,与B6小鼠相比,C3小鼠的心率始终高出约80次/分钟。在本研究中,我们假设在接触PM期间,C3和B6小鼠在交感神经和副交感神经对心率的控制平衡方面存在差异。将无线电遥测仪植入C3和B6小鼠体内,以测量在连续3小时暴露于过滤空气(FA)或炭黑(CB,<300微克/立方米)期间的心率反应和心率变异性(HRV)参数。在给予生理盐水或副交感神经(PS;阿托品,0.5毫克/千克腹腔注射)和交感神经(S;普萘洛尔,1毫克/千克腹腔注射)阻断后重复进行暴露,以研究CB暴露期间心率的自主调节。在生理盐水的FA暴露期间,与B6小鼠相比,C3小鼠的3小时平均心率反应(次/分钟±标准误)显著更高(p<0.05)(496±22对427±3)。使用PS阻断后,C3和B6小鼠之间的品系差异不明显(485±23对503±61)。使用S阻断后,与生理盐水相比,C3小鼠的3小时平均心率反应显著降低(p<0.05)(B6小鼠为413±18对392±15)。在生理盐水的CB暴露期间,与B6小鼠相比,C3小鼠的心率反应再次显著升高(p<0.05),但这些心率反应与FA暴露相比没有差异。使用S阻断后,与FA相比,B6小鼠在CB暴露期间的心率显著升高(p<0.05),但C3小鼠的心率没有变化。总体而言,这些结果表明,心率调节的品系差异是由于B6小鼠中明显的强大副交感神经张力和C3小鼠中占主导地位的交感神经张力。此外,CB暴露通过调节副交感神经张力的减弱来改变B6小鼠的心率调节。最后,B6和C3小鼠在对急性PM暴露的心率反应方面的品系差异意味着强大的遗传决定因素调节了易感个体中自主调节的改变。