Fabris G, Anselmo-Franci J A, Branco L G
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 1999 Nov;32(11):1389-98. doi: 10.1590/s0100-879x1999001100009.
Hypoxia elicits hyperventilation and hypothermia, but the mechanisms involved are not well understood. The nitric oxide (NO) pathway is involved in hypoxia-induced hypothermia and hyperventilation, and works as a neuromodulator in the central nervous system, including the locus coeruleus (LC), which is a noradrenergic nucleus in the pons. The LC plays a role in a number of stress-induced responses, but its participation in the control of breathing and thermoregulation is unclear. Thus, in the present study, we tested the hypothesis that LC plays a role in the hypoxia-induced hypothermia and hyperventilation, and that NO is involved in these responses. Electrolytic lesions were performed bilaterally within the LC in awake unrestrained adult male Wistar rats weighing 250-350 g. Body temperature and pulmonary ventilation (V E) were measured. The rats were divided into 3 groups: control (N = 16), sham operated (N = 7) and LC lesioned (N = 19), and each group received a saline or an N G-nitro-L-arginine methyl ester (L-NAME, 250 microg/microl) intracerebroventricular (icv) injection. No significant difference was observed between control and sham-operated rats. Hypoxia (7% inspired O2) caused hyperventilation and hypothermia in both control (from 541.62 +/- 35.02 to 1816.18 +/- 170.7 and 36.3 +/- 0.12 to 34. 4 +/- 0.09, respectively) and LC-lesioned rats (LCLR) (from 694.65 +/- 63.17 to 2670.29 +/- 471.33 and 36 +/- 0.12 to 35.3 +/- 0.12, respectively), but the increase in V E was higher (P<0.05) and hypothermia was reduced (P<0.05) in LCLR. L-NAME caused no significant change in V E or in body temperature under normoxia, but abolished both the hypoxia-induced hyperventilation and hypothermia. Hypoxia-induced hyperventilation was reduced in LCLR treated with L-NAME. L-NAME also abolished the hypoxia-induced hypothermia in LCLR. The present data indicate that hypoxia-induced hyperventilation and hypothermia may be related to the LC, and that NO is involved in these responses.
缺氧会引发过度通气和体温过低，但其中涉及的机制尚未完全明确。一氧化氮（NO）途径参与了缺氧诱导的体温过低和过度通气，并在中枢神经系统中作为一种神经调节剂发挥作用，包括蓝斑（LC），它是脑桥中的一个去甲肾上腺素能核团。LC在许多应激诱导的反应中起作用，但其在呼吸控制和体温调节中的参与情况尚不清楚。因此，在本研究中，我们测试了以下假设：LC在缺氧诱导的体温过低和过度通气中起作用，并且NO参与了这些反应。对体重250 - 350克的清醒无拘束成年雄性Wistar大鼠双侧进行LC内的电解损伤。测量体温和肺通气量（VE）。将大鼠分为3组：对照组（N = 16）、假手术组（N = 7）和LC损伤组（N = 19），每组接受生理盐水或N G - 硝基 - L - 精氨酸甲酯（L - NAME，250微克/微升）的脑室内（icv）注射。对照组和假手术组大鼠之间未观察到显著差异。缺氧（吸入7% O2）在对照组（分别从541.62±35.02到1816.18±170.7以及从36.3±0.12到34.4±0.09）和LC损伤大鼠（LCLR）（分别从694.65±63.17到2670.29±471.33以及从36±0.12到35.3±0.12）中均导致过度通气和体温过低，但LCLR中VE的增加更高（P<0.05）且体温过低程度减轻（P<0.05）。在常氧条件下，L - NAME对VE或体温无显著影响，但消除了缺氧诱导的过度通气和体温过低。用L - NAME处理的LCLR中，缺氧诱导的过度通气减少。L - NAME也消除了LCLR中缺氧诱导的体温过低。目前的数据表明，缺氧诱导的过度通气和体温过低可能与LC有关，并且NO参与了这些反应。
