Ye S, Mozayeni P, Gamburd M, Zhong H, Campese V M
Division of Nephrology, Department of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2786-96. doi: 10.1152/ajpheart.2000.279.6.H2786.
Increased sympathetic nervous system (SNS) activity plays a role in the genesis of hypertension in rats with chronic renal failure (CRF). The rise in central SNS activity is mitigated by increased local expression of neuronal nitric oxide synthase (NOS) mRNA and NO(2)/NO(3) production. Because interleukin (IL)-1beta may activate nitric oxide in the brain, we have tested the hypothesis that IL-1beta may modulate the activity of the SNS via regulation of the local expression of neuronal NOS (nNOS) in the brain of CRF and control rats. To this end, we first found that administration of IL-1beta in the lateral ventricle of control and CRF rats decreased blood pressure and norepinephrine (NE) secretion from the posterior hypothalamus (PH) and increased NOS mRNA expression. Second, we observed that an acute or chronic injection of an IL-1beta-specific antibody in the lateral ventricle raised blood pressure and NE secretion from the PH and decreased NOS mRNA abundance in the PH of control and CRF rats. Finally, we measured the IL-1beta mRNA abundance in the PH, locus coeruleus, and paraventricular nuclei of CRF and control rats by RT-PCR and found it to be greater in CRF rats than in control rats. In conclusion, these studies have shown that IL-1beta modulates the activity of the SNS in the central nervous system and that this modulation is mediated by increased local expression of nNOS mRNA.
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。中枢SNS活性的升高可通过神经元型一氧化氮合酶（NOS）mRNA局部表达增加和NO(2)/NO(3)生成增加而减轻。由于白细胞介素（IL）-1β可能激活脑中的一氧化氮，我们检验了这样一个假说，即IL-1β可能通过调节CRF大鼠和对照大鼠脑中神经元型NOS（nNOS）的局部表达来调节SNS的活性。为此，我们首先发现，向对照大鼠和CRF大鼠侧脑室内注射IL-1β可降低血压和下丘脑后部（PH）去甲肾上腺素（NE）的分泌，并增加NOS mRNA表达。其次，我们观察到，向对照大鼠和CRF大鼠侧脑室内急性或慢性注射IL-1β特异性抗体可升高血压和PH中NE的分泌，并降低PH中NOS mRNA丰度。最后，我们通过逆转录聚合酶链反应（RT-PCR）测量了CRF大鼠和对照大鼠PH、蓝斑和室旁核中IL-1β mRNA丰度，发现CRF大鼠中的丰度高于对照大鼠。总之，这些研究表明，IL-1β调节中枢神经系统中SNS的活性，且这种调节是由nNOS mRNA局部表达增加介导的。
