Pechanova Olga, Vrankova Stanislava, Cebova Martina
Centre of Experimental Medicine, Slovak Academy of Sciences, Institute of Normal and Pathological Physiology, 813 71 Bratislava, Slovakia.
Pathophysiology. 2020 Dec 15;27(1):46-54. doi: 10.3390/pathophysiology27010007.
The goal of our study was to analyze the time course of the effect of N-nitro-L-arginine methyl ester (L-NAME) on nitric oxide synthase (NOS) isoforms and nuclear factor-κB (NF-κB) protein expression, total NOS activity, and blood pressure (BP) in rats. Adult 12-week-old male Wistar rats were subjected to treatment with L-NAME (40 mg/kg/day) for four and seven weeks. BP was increased after 4- and 7-week L-NAME treatments. NOS activity decreased after 4-week-L-NAME treatment; however, the 7-week treatment increased NOS activity in the aorta, heart, and kidney, while it markedly decreased NOS activity in the brainstem, cerebellum, and brain cortex. The 4-week-L-NAME treatment increased eNOS expression in the aorta, heart, and kidney and this increase was amplified after 7 weeks of treatment. In the brain regions, eNOS expression remained unchanged after 4-week L-NAME treatment and prolonged treatment led to a significant decrease of eNOS expression in these tissues. NF-κB expression increased in both peripheral and brain tissues after 4 weeks of treatment and prolongation of treatment decreased the expression in the aorta, heart, and kidney. In conclusion, decreased expression of eNOS in the brain regions after 7-week L-NAME treatment may be responsible for a remarkable decrease of NOS activity in these regions. Since the BP increase persisted after 7 weeks of L-NAME treatment, we hypothesize that central regulation of BP may contribute significantly to L-NAME-induced hypertension.
我们研究的目的是分析N-硝基-L-精氨酸甲酯（L-NAME）对大鼠一氧化氮合酶（NOS）亚型、核因子-κB（NF-κB）蛋白表达、总NOS活性及血压（BP）影响的时间进程。12周龄成年雄性Wistar大鼠接受L-NAME（40mg/kg/天）治疗4周和7周。L-NAME治疗4周和7周后血压升高。L-NAME治疗4周后NOS活性降低；然而，7周治疗使主动脉、心脏和肾脏中的NOS活性增加，而使脑干、小脑和大脑皮层中的NOS活性显著降低。L-NAME治疗4周后主动脉、心脏和肾脏中内皮型一氧化氮合酶（eNOS）表达增加，且这种增加在治疗7周后进一步放大。在脑区，L-NAME治疗4周后eNOS表达未改变，长期治疗导致这些组织中eNOS表达显著降低。治疗4周后外周和脑组织中NF-κB表达均增加，延长治疗则使主动脉、心脏和肾脏中的表达降低。总之，L-NAME治疗7周后脑区eNOS表达降低可能是这些区域NOS活性显著降低的原因。由于L-NAME治疗7周后血压升高持续存在，我们推测血压的中枢调节可能对L-NAME诱导的高血压有显著影响。
