Curtis A L, Drolet G, Valentino R J
Department of Mental Health Sciences, Hahnemann University, Philadelphia, PA 19102-1192.
Brain Res Bull. 1993;31(6):737-44. doi: 10.1016/0361-9230(93)90150-a.
The effects of hypotensive stress elicited by nitroprusside infusion on discharge activity of noradrenergic locus coeruleus (LC) neurons of unanesthetized rats were characterized. Nitroprusside (75 micrograms/30 microliters/min, 15 min IV infusion) decreased mean arterial pressure of unanesthetized rats by 50 +/- 2 mmHg (n = 5). Simultaneous recordings of LC spontaneous discharge revealed an increase in discharge rate (197 +/- 87%) that was associated with hypotension. A lower concentration of nitroprusside (10 micrograms/30 microliters/min) that decreased blood pressure of halothane-anesthetized rats by 55 +/- 2 mmHg was much less effective in producing hypotension and did not increase LC discharge when administered to unanesthetized rats. Prior administration of the CRF antagonist, alpha helical CRF9-41 (50 micrograms, ICV) greatly attenuated LC activation by nitroprusside. These findings demonstrate that LC activation elicited by nitroprusside is dependent on the magnitude of hypotension. The present results also demonstrate that nitroprusside is a less potent hemodynamic challenge in unanesthetized rats. Finally, LC activation associated with nitroprusside administration to unanesthetized rats is mediated to a large extent by CRF, confirming findings in anesthetized rats.
研究了硝普钠输注引起的低血压应激对未麻醉大鼠去甲肾上腺素能蓝斑（LC）神经元放电活动的影响。硝普钠（75微克/30微升/分钟，静脉输注15分钟）使未麻醉大鼠的平均动脉压降低了50±2毫米汞柱（n = 5）。同时记录LC自发放电发现放电率增加（197±87%），这与低血压有关。较低浓度的硝普钠（10微克/30微升/分钟）使氟烷麻醉大鼠的血压降低了55±2毫米汞柱，但对未麻醉大鼠产生低血压的效果要差得多，且给药时不会增加LC放电。预先给予促肾上腺皮质激素释放因子（CRF）拮抗剂α螺旋CRF9 - 41（50微克，脑室内注射）可大大减弱硝普钠对LC的激活作用。这些发现表明，硝普钠引起的LC激活取决于低血压的程度。目前的结果还表明，硝普钠对未麻醉大鼠是一种效力较弱的血流动力学刺激。最后，给未麻醉大鼠注射硝普钠相关的LC激活在很大程度上由CRF介导，这证实了在麻醉大鼠中的发现。
