Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Denmark.
Am J Physiol Renal Physiol. 2012 Sep 15;303(6):F855-63. doi: 10.1152/ajprenal.00026.2012. Epub 2012 Jul 18.
Connexins in renal arterioles affect autoregulation of arteriolar tonus and renal blood flow and are believed to be involved in the transmission of the tubuloglomerular feedback (TGF) response across the cells of the juxtaglomerular apparatus. Connexin40 (Cx40) also plays a significant role in the regulation of renin secretion. We investigated the effect of deleting the Cx40 gene on autoregulation of afferent arteriolar diameter in response to acute changes in renal perfusion pressure. The experiments were performed using the isolated blood perfused juxtamedullary nephron preparation in kidneys obtained from wild-type or Cx40 knockout mice. Renal perfusion pressure was increased in steps from 75 to 155 mmHg, and the response in afferent arteriolar diameter was measured. Hereafter, a papillectomy was performed to inhibit TGF, and the pressure steps were repeated. Conduction of intercellular Ca(2+) changes in response to local electrical stimulation was examined in isolated interlobular arteries and afferent arterioles from wild-type or Cx40 knockout mice. Cx40 knockout mice had an impaired autoregulatory response to acute changes in renal perfusion pressure compared with wild-type mice. Inhibition of TGF by papillectomy significantly reduced autoregulation of afferent arteriolar diameter in wild-type mice. In Cx40 knockout mice, papillectomy did not affect the autoregulatory response, indicating that these mice have no functional TGF. Also, Cx40 knockout mice showed no conduction of intercellular Ca(2+) changes in response to local electrical stimulation of interlobular arteries, whereas the Ca(2+) response to norepinephrine was unaffected. These results suggest that Cx40 plays a significant role in the renal autoregulatory response of preglomerular resistance vessels.
缝隙连接蛋白存在于肾小动脉中，可影响小动脉张力和肾血流量的自身调节，并且被认为参与了跨肾小球旁器细胞的管-球反馈（TGF）反应的传递。连接蛋白 40（Cx40）在调节肾素分泌方面也起着重要作用。我们研究了删除 Cx40 基因对肾灌注压急性变化时入球小动脉直径自身调节的影响。该实验使用从野生型或 Cx40 敲除小鼠获得的肾分离的血灌注髓旁肾单位制备物进行。将肾灌注压分阶段从 75mmHg 增加到 155mmHg，并测量入球小动脉直径的反应。此后，进行乳头切除术以抑制 TGF，并重复压力阶跃。在野生型或 Cx40 敲除小鼠的分离的小叶间动脉和入球小动脉中检查了细胞间 Ca2+变化的电刺激传递。与野生型小鼠相比，Cx40 敲除小鼠对肾灌注压急性变化的自身调节反应受损。乳头切除术抑制 TGF 显著降低了野生型小鼠入球小动脉直径的自身调节。在 Cx40 敲除小鼠中，乳头切除术不影响自身调节反应，表明这些小鼠没有功能性的 TGF。此外，Cx40 敲除小鼠对小叶间动脉局部电刺激无细胞间 Ca2+变化的传递，而对去甲肾上腺素的 Ca2+反应不受影响。这些结果表明，Cx40 在肾小球前阻力血管的肾自身调节反应中起着重要作用。
