Supplemental Digital Content is available in the text. Impaired renal autoregulation permits more transmission of disturbance in systemic blood pressure, which initiates barotrauma in intrarenal microvasculatures such as glomerular and tubulointerstitial capillaries, contributing to the development of kidney damage and deterioration in renal function, especially under the conditions with high blood pressure. Although it has been postulated that autoregulatory efficiency is attenuated in the aging kidney, direct evidence remains lacking. In the present study, we measured the autoregulation of renal blood flow, myogenic response of afferent arteriole (Af-Art), tubuloglomerular feedback in vivo with micropuncture, as well as tubuloglomerular feedback in vitro in isolated perfused juxtaglomerular apparatus in young and aged C57BL/6 mice. We found that renal blood flow was not significantly changed in response to a defined elevation of renal arterial pressure in young mice but significantly increased in aged mice. Additionally, myogenic response of Af-Art measured by microperfusion with a stepwise increase in perfusion pressure was significantly blunted in the aging kidney, which is associated with the attenuation of intraluminal pressure-induced intracellular calcium increases, as well as the reduced expression of integrin α5 (Itga5) in Af-Art. Moreover, both tubuloglomerular feedback in vivo and in vitro were nearly inactive in the aging kidney, which is associated with the significantly reduced expression of adenosine A1 receptor (A1AR) and suppressed vasoconstrictor response to adenosine in Af-Art. In conclusion, this study demonstrates that aging impairs renal autoregulation with blunted myogenic response and inhibited tubuloglomerular feedback response. The underlying mechanisms involve the downregulations of integrin α5 and A1AR in the Af-Art.

中文翻译：

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衰老会损害小鼠的肾脏自动调节

补充数字内容在文本中可用。受损的肾脏自动调节允许更多的全身血压紊乱传递，这会引发肾内微血管（如肾小球和肾小管间质毛细血管）的气压伤，导致肾损伤和肾功能恶化，尤其是在高血压条件下。尽管有人假设衰老肾脏的自动调节效率会减弱，但仍然缺乏直接证据。在本研究中，我们测量了肾血流量的自动调节、传入小动脉 (Af-Art) 的肌原性反应、微穿刺的体内肾小球反馈，以及年轻和老年 C57BL/ 6只老鼠。我们发现，年轻小鼠肾动脉压升高时，肾血流量没有显着变化，但老年小鼠显着增加。此外，通过逐步增加灌注压力的微灌注测量的 Af-Art 的肌原性反应在老化的肾脏中显着减弱，这与管腔内压力诱导的细胞内钙增加的减弱以及整合素 α5 的表达降低有关(Itga5) 在 Af-Art 中。此外，体内和体外的肾小球反馈在衰老肾脏中几乎没有活性，这与腺苷 A1 受体 (A1AR) 的表达显着降低和抑制 Af-Art 中对腺苷的血管收缩反应有关。综上所述，这项研究表明，衰老会削弱肾脏的自动调节功能，减弱肌源性反应并抑制肾小球反馈反应。潜在机制涉及 Af-Art 中整合素 α5 和 A1AR 的下调。