Ye S, Nosrati S, Campese V M
Department of Medicine, University of Southern California, Los Angeles 90033, USA.
J Clin Invest. 1997 Feb 1;99(3):540-8. doi: 10.1172/JCI119191.
Increased sympathetic nervous system (SNS) activity plays a role in the genesis of hypertension in rats with chronic renal failure (CRF). Because nitric oxide (NO) modulates the activity of the SNS, a deficit of NO synthesis could be responsible for the increased SNS activity in these animals. In the present study, we evaluated the effects of L-arginine and L-NAME on blood pressure and SNS activity-in Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS activity was determined by measuring norepinephrine turnover rate in several brain nuclei involved in the regulation of blood pressure. In the same brain nuclei, we measured NO content and nitric oxide synthase (NOS) gene expression by semiquantitative measurements of NOS mRNA reverse transcription polymerase chain reaction. In CRF rats, norepinephrine turnover rate was increased in the posterior hypothalamic nuclei, locus coeruleus, paraventricular nuclei, and the rostral ventral medulla, whereas NOS mRNA gene expression and NO2/NO3 content were increased in all brain nuclei tested. L-NAME increased blood pressure and NE turnover rate in several brain nuclei of both control and 5/6 nephrectomized rats. In CRF rats, a significant relationship was present between the percent increment in NOS mRNA gene expression related to the renal failure, and the percent increase in norepinephrine turnover rate caused by L-NAME. This suggests that endogenous NO may partially inhibit the activity of the SNS in brain nuclei involved in the neurogenic regulation of blood pressure, and this inhibition is enhanced in CRF rats. In summary, the increase in SNS activity in the posterior hypothalamic nuclei and in the locus coeruleus of CRF rats is partially mitigated by increased local expression of NOS m-RNA.
交感神经系统（SNS）活性增加在慢性肾衰竭（CRF）大鼠高血压的发生中起作用。由于一氧化氮（NO）调节SNS的活性，NO合成不足可能是这些动物SNS活性增加的原因。在本研究中，我们评估了L-精氨酸和L- NAME对Sprague Dawley 5/6肾切除或假手术大鼠血压和SNS活性的影响。通过测量参与血压调节的几个脑核中去甲肾上腺素周转率来确定SNS活性。在相同的脑核中，我们通过对NOS mRNA逆转录聚合酶链反应的半定量测量来测量NO含量和一氧化氮合酶（NOS）基因表达。在CRF大鼠中，下丘脑后核、蓝斑、室旁核和延髓头端腹内侧去甲肾上腺素周转率增加，而在所有测试的脑核中NOS mRNA基因表达和NO2/NO3含量增加。L- NAME增加了对照和5/6肾切除大鼠几个脑核的血压和NE周转率。在CRF大鼠中，与肾衰竭相关的NOS mRNA基因表达增加百分比与L- NAME引起的去甲肾上腺素周转率增加百分比之间存在显著关系。这表明内源性NO可能部分抑制参与血压神经源性调节的脑核中SNS的活性，并且这种抑制在CRF大鼠中增强。总之，CRF大鼠下丘脑后核和蓝斑中SNS活性的增加被NOS m-RNA局部表达的增加部分减轻。
