Khraibi A A, Ramsey C R, Heublein D M, Berndt T J, Knox F G
Department of Obstetrics and Gynecology, The University of Illinois at Chicago, 60612-7313, USA.
Life Sci. 2001 Jul 27;69(10):1123-31. doi: 10.1016/s0024-3205(01)01184-5.
The objective of this study was to determine the effect of N(G)-monomethyl-L-arginine (L-NMMA) infusion on plasma renin activity (PRA) in the presence or absence of the renal nerves in normotensive Wistar-Kyoto (WKY) rats and Okamoto spontaneously hypertensive rats (SHR). All rats were unilaterally nephrectomized two weeks before the acute experiment. On the day of the experiment, acute renal denervation (Dnx) of the remaining kidney was performed in one group of WKY rats (Dnx-WKY; n= 10) and one group of SHRs (Dnx-SHR: n=7). The renal nerves were left intact in a group of WKY rats (Inn-WKY; n=8) and SHRs (Inn-SHR; n=9). After a control clearance period, L-NMMA was administered i.v. (15 mg/kg bolus followed by 500 microg/kg/min infusion) and another clearance period of 20 min was taken. In all experimental groups L-NMMA infusion resulted in a significant natriuresis. L-NMMA infusion increased fractional excretion of sodium (FE(Na)) to a greater extent in the Inn-SHR than in the Inn-WKY (delta FE(Na) = 5.23+/-0.87% vs delta FE(Na) = 2.87+/-0.73% respectively; P=0.05), PRA did not change in the SHR with the infusion of L-NMMA. However, in the Inn-WKY group, the natriuresis of L-NMMA infusion was associated with a tendency for lower PRA levels as compared to a group of time control Inn-WKY rats. In Dnx-WKY, the natriuresis of L-NMMA infusion (delta FE(Na) = 4.60+/-0.52%) was associated with a significantly lower level of PRA (4.26+/-1.18 ng AI/ml/hr) as compared to a group of time control Dnx-WKY rats (9.83+/-1.32 ng AI/ml/hr; P<0.05). In the Dnx-SHR, the natriuretic response to L-NMMA infusion was significantly attenuated by renal denervation (delta FE(Na) = 2.36+/-0.34%) and PRA was unchanged. In conclusion, the natriuretic effect of systemic inhibition of nitric oxide (NO) synthesis was associated with decreased PRA in the Dnx-WKY suggesting that a potential interaction exists between NO and the renal nerves in the modulation of PRA in the normotensive WKY rat. Whereas, the natriuretic effect of L-NMMA infusion in the SHR in the presence and absence of the renal nerves, were independent of changes in PRA.
本研究的目的是确定在正常血压的Wistar-Kyoto(WKY)大鼠和冈本自发性高血压大鼠(SHR)中,输注N(G)-单甲基-L-精氨酸(L-NMMA)对血浆肾素活性(PRA)的影响,实验分别在保留或去除肾神经的情况下进行。所有大鼠在急性实验前两周进行单侧肾切除。实验当天,一组WKY大鼠(Dnx-WKY;n = 10)和一组SHR(Dnx-SHR:n = 7)对剩余肾脏进行急性肾去神经支配(Dnx)。一组WKY大鼠(Inn-WKY;n = 8)和SHR(Inn-SHR;n = 9)保留完整的肾神经。在一个对照清除期后,静脉注射L-NMMA(15 mg/kg推注,随后以500 μg/kg/min输注),并再进行20分钟的清除期。在所有实验组中,输注L-NMMA均导致显著的利钠作用。与Inn-WKY组相比,Inn-SHR组输注L-NMMA后钠分数排泄(FE(Na))增加幅度更大(分别为ΔFE(Na) = 5.23±0.87% 与 ΔFE(Na) = 2.87±0.73%;P = 0.05),SHR输注L-NMMA后PRA没有变化。然而,在Inn-WKY组中,与一组时间对照的Inn-WKY大鼠相比,输注L-NMMA后的利钠作用与PRA水平降低的趋势相关。在Dnx-WKY组中,与一组时间对照的Dnx-WKY大鼠(9.83±1.32 ng AI/ml/hr;P<0.05)相比,输注L-NMMA后的利钠作用(ΔFE(Na) = 4.60±0.52%)与显著降低PRA水平(4.26±1.18 ng AI/ml/hr)相关。在Dnx-SHR组中,肾去神经支配显著减弱了对L-NMMA输注的利钠反应(ΔFE(Na) = 2.36±0.34%),而PRA没有变化。总之,在Dnx-WKY组中,系统性抑制一氧化氮(NO)合成的利钠作用与PRA降低相关,这表明在正常血压的WKY大鼠中,NO与肾神经在调节PRA方面可能存在潜在相互作用。而在有或无肾神经的情况下,SHR输注L-NMMA的利钠作用与PRA变化无关。