Moe O W, Ujiie K, Star R A, Miller R T, Widell J, Alpern R J, Henrich W L
Department of Internal Medicine, University of Texas Southwestern, Dallas 75230.
J Clin Invest. 1993 Mar;91(3):774-9. doi: 10.1172/JCI116296.
Angiotensinogen, angiotensin-converting enzyme, and renin constitute the components of the renin-angiotensin system. The mammalian renal proximal tubule contains angiotensinogen, angiotensin-converting enzyme, and angiotensin receptors. Previous immunohistochemical studies describing the presence of renin in the proximal tubule could not distinguish synthesized renin from renin trapped from the glomerular filtrate. In the present study, we examined the presence of renin activity and mRNA in rabbit proximal tubule cells in primary culture and renin mRNA in microdissected proximal tubules. Renin activity was present in lysates of proximal tubule cells in primary culture. Cellular renin content in cultured proximal tubule cells was increased by incubation with 10(-5) M isoproterenol and 10(-5) M forskolin by 150 and 110%, respectively. In addition, renin transcripts were detected in poly(A)+ RNA from cultured proximal tubule cells by RNA blots under high stringency conditions. In microdissected tubules from normal rats, renin mRNA was not detectable with reverse transcription and polymerase chain reaction. However, in tubules from rats administered the angiotensinogen-converting-enzyme inhibitor, enalapril, renin was easily detected in the S2 segment of the proximal tubule. We postulate the existence of a local renin-angiotensin system that enables the proximal tubule to generate angiotensin II, thereby providing an autocrine system that could locally modulate NaHCO3 and NaCl absorption.
血管紧张素原、血管紧张素转换酶和肾素构成了肾素-血管紧张素系统的组成部分。哺乳动物的肾近端小管含有血管紧张素原、血管紧张素转换酶和血管紧张素受体。以往描述肾近端小管中存在肾素的免疫组织化学研究无法区分合成的肾素和从肾小球滤液中捕获的肾素。在本研究中,我们检测了原代培养的兔近端小管细胞中肾素活性和mRNA的存在情况,以及显微解剖的近端小管中肾素mRNA的存在情况。原代培养的近端小管细胞裂解物中存在肾素活性。用10^(-5)M异丙肾上腺素和10^(-5)M福斯可林孵育后,培养的近端小管细胞中的细胞肾素含量分别增加了150%和110%。此外,在高严格条件下通过RNA印迹法在培养的近端小管细胞的聚腺苷酸加尾RNA中检测到了肾素转录本。在正常大鼠的显微解剖小管中,通过逆转录和聚合酶链反应无法检测到肾素mRNA。然而,在给予血管紧张素原转换酶抑制剂依那普利的大鼠的小管中,很容易在近端小管的S2段检测到肾素。我们推测存在一个局部肾素-血管紧张素系统,该系统使近端小管能够生成血管紧张素II,从而提供一个可以局部调节NaHCO3和NaCl重吸收的自分泌系统。