Bigazzi R, Kogosov E, Campese V M
Department of Medicine, University of Southern California, Los Angeles.
J Am Soc Nephrol. 1994 May;4(11):1901-7. doi: 10.1681/ASN.V4111901.
Disturbances of the sympathetic nervous system have been described in chronic renal failure, but their role in the genesis and maintenance of hypertension frequently associated with this condition has not been established. The neuroadrenergic activity in brain nuclei involved in the regulation of blood pressure in uremic animals has also not been previously evaluated. In these studies, the neuroadrenergic activity was measured in the anterior, lateral, and posterior hypothalamic nuclei, in the locus coeruleus, and in the nucleus tractus solitarius of Sprague Dawley rats 5/6 nephrectomized or sham operated 4 wk before the experiments. Neuroadrenergic activity was determined by calculating norepinephrine (NE) turnover rate (in picograms per milligram per hour), 3, 6 and 12 h after inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly greater in the posterior hypothalamic nuclei (21,501 +/- 1,777 pg/mg wet wt) and in the locus coeruleus (16,152 +/- 1,114 pg/mg wet tissue) of uremic compared with control rats (12,213 +/- 1,404 and 7,991 +/- 622 pg/mg wet wt, respectively). On the other hand, the endogenous NE content of the nucleus tractus solitarius and the anterior hypothalamic nuclei did not differ between uremic and control rats. The turnover rate of NE in the posterior hypothalamic nuclei of uremic rats (2150 +/- 430 pg/mg per hour) was significantly faster (P < 0.05) than in control rats (977 +/- 244 pg/mg per hour). The turnover rate of NE in the locus coeruleus of uremic rats (2,584 +/- 323 pg/mg per hour) was also significantly faster than in control animals (400 +/- 140 pg/mg per hour; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
慢性肾衰竭中已描述了交感神经系统紊乱,但它们在常与此病症相关的高血压的发生和维持中的作用尚未明确。此前也未评估尿毒症动物中参与血压调节的脑核中的神经肾上腺素能活性。在这些研究中,于实验前4周对行5/6肾切除术或假手术的Sprague Dawley大鼠的下丘脑前核、外侧核和后核、蓝斑以及孤束核中的神经肾上腺素能活性进行了测量。通过计算用L-甲基酪氨酸抑制去甲肾上腺素(NE)合成后3、6和12小时的NE周转率(皮克/毫克/小时)来确定神经肾上腺素能活性。与对照大鼠相比,尿毒症大鼠下丘脑后核(21,501±1,777皮克/毫克湿重)和蓝斑(16,152±1,114皮克/毫克湿组织)中的内源性NE浓度显著更高(对照大鼠分别为12,213±1,404和7,991±622皮克/毫克湿重)。另一方面,尿毒症大鼠和对照大鼠的孤束核及下丘脑前核的内源性NE含量无差异。尿毒症大鼠下丘脑后核中NE的周转率(2150±430皮克/毫克/小时)显著快于对照大鼠(977±244皮克/毫克/小时;P<0.05)。尿毒症大鼠蓝斑中NE的周转率(2,584±323皮克/毫克/小时)也显著快于对照动物(400±140皮克/毫克/小时;P<0.01)。(摘要截断于250字)