Neuronal NOS contributes to biphasic autoregulatory response during enhanced TGF activity
Neuronal NOS contributes to biphasic autoregulatory response during enhanced TGF activity
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DOI：
10.1152/ajprenal.1999.277.1.f113
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发表时间：
1999-07-01
影响因子：
4.2
通讯作者：
Navar, LG
中科院分区：
文献类型：
--
作者：
Ichihara, A;Navar, LG
为了评估传入小动脉的自动调节反应，在活动增加的肾小管肾小球反馈（TGF）机制，并描绘神经元型一氧化氮合酶（nNOS）的贡献，这种反应，传入小动脉直径反应的变化，肾灌注压（RPP）进行了监测，在体外使用血液灌注的大鼠延髓肾单位制备。在RPP为100 mmHg时，基底传入小动脉直径平均为21.1 ± 1.4 μ m（n = 9）。传入小动脉对RPP增加60 mmHg的初始和持续收缩反应平均分别为14.8 +/- 1.4%和13.3 +/-1.3%。乙酰唑胺治疗通过增加远端肾单位的体积输送来增强TGF的反应性，使基底传入小动脉直径显著降低8.2 ± 0.5%，并增强了对RPP增加60 mmHg的初始反应（25.5 ± 2.3%），但没有改变持续反应（14.3 ± 1.5%）。在另一系列实验中，用10 μ M S-甲基-L-硫代瓜氨酸（L-SMTC）抑制nNOS，可显著降低传入小动脉直径，从20.3 +/- 1.3 μ m降至18.3 +/- 1.1 μ m（n = 7），并增强初始的（34.4 +/- 3.5%）和持续收缩反应（27.6 +/- 2.9%），以60 mmHg的RPP增加。乙酰唑胺治疗进一步增强了初始（56.4 +/- 3.0%）和持续应答（54.6 +/- 2.7%）。通过切断Henle环中断远端递送防止了对乙酰唑胺或L-SMTC引起的RPP增加的增强反应。这些结果表明，nNOS有助于通过TGF依赖性机制的反作用复位过程的双相传入小动脉收缩反应增加RPP。
To assess the afferent arteriolar autoregulatory response during increased activity of the tubuloglomerular feedback (TGF) mechanism and to delineate the contribution of neuronal nitric oxide synthase (nNOS) to this response, afferent arteriolar diameter responses to changes in renal perfusion pressure (RPP) were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. At RPP of 100 mmHg, basal afferent arteriolar diameter averaged 21.1 +/- 1.4 mu m (n = 9). The initial and sustained constrictor responses of afferent arterioles to a 60-mmHg increase in RPP averaged 14.8 +/- 1.4% and 13.3 +/- 1.3%, respectively. Acetazolamide treatment, which enhances TGF responsiveness by increasing distal nephron volume delivery, significantly decreased basal afferent arteriolar diameter by 8.2 +/- 0.5% and enhanced the initial response (25.5 +/- 2.3%) to a 60-mmHg increase in RPP but did not alter the sustained response (14.3 +/- 1.5%). In another series of experiments, nNOS inhibition with 10 mu M S-methyl-L-thiocitrulline (L-SMTC) significantly decreased afferent arteriolar diameter from 20.3 +/- 1.3 to 18.3 +/- 1.1 mu m (n = 7) and enhanced both the initial (34.4 +/- 3.5%) and sustained constrictor responses (27.6 +/- 2.9%) to a 60-mmHg increase in RPP. Treatment with acetazolamide further enhanced both initial (56.4 +/- 3.0%) and sustained responses (54.6 +/- 2.7%). Interruption of distal delivery by transection of the loops of Henle prevented the enhanced responses to increases in RPP elicited with either acetazolamide or L-SMTC. These results indicate that nNOS contributes to the counteracting resetting process of biphasic afferent arteriolar constrictor responses to increases in RPP through a TGF-dependent mechanism.