He X R, Greenberg S G, Briggs J P, Schnermann J
Department of Physiology, University of Michigan, Ann Arbor 48109, USA.
Hypertension. 1995 Jul;26(1):137-42. doi: 10.1161/01.hyp.26.1.137.
The present studies in perfused specimens of the juxtaglomerular apparatus microdissected from rabbit kidneys were performed to quantitatively evaluate the relation between macula densa NaCl concentration and renin secretion and to study the effect of furosemide and verapamil on NaCl dependency of renin release. Renin secretion was found to decrease exponentially when macula densa NaCl concentration was increased from 26/7 mmol/L (Na/Cl) to 46/27, 66/47, and 86/67 mmol/L. Increasing Na/Cl concentrations from 86/67 to 106/87 mmol/L had no further effect on renin secretion. [Cl]1/2, the chloride concentration producing the half-maximal effect, was 30 mmol/L. Addition of 50 mumol/L furosemide to the luminal fluid caused renin secretion to become essentially independent of macula densa NaCl concentration. This effect was due to both an increase of renin secretion at high NaCl concentrations and a decrease of renin release at low NaCl concentrations. Verapamil added to the superfusate at a concentration of 1 mumol/L also abolished NaCl dependency of renin secretion; most of this effect was due to an increase of renin release at high luminal NaCl. These results suggest that Na-2Cl-K cotransport and calcium flux through voltage-gated channels are two mechanisms required for the expression of NaCl-dependent renin release. Identification of the cellular localizations of these two critical membrane proteins in the renin control pathway requires further study.
本研究采用从兔肾显微解剖的肾素-血管紧张素系统灌注标本，旨在定量评估致密斑氯化钠浓度与肾素分泌之间的关系，并研究呋塞米和维拉帕米对肾素释放的氯化钠依赖性的影响。当致密斑氯化钠浓度从26/7 mmol/L（钠/氯）增加到46/27、66/47和86/67 mmol/L时，发现肾素分泌呈指数下降。将钠/氯浓度从86/67 mmol/L增加到106/87 mmol/L对肾素分泌没有进一步影响。产生半数最大效应的氯浓度[Cl]1/2为30 mmol/L。向管腔液中添加50 μmol/L呋塞米可使肾素分泌基本上与致密斑氯化钠浓度无关。这种效应是由于高氯化钠浓度下肾素分泌增加以及低氯化钠浓度下肾素释放减少所致。以1 μmol/L的浓度添加到灌流液中的维拉帕米也消除了肾素分泌的氯化钠依赖性；这种效应大部分是由于高管腔氯化钠浓度下肾素释放增加所致。这些结果表明，Na-2Cl-K共转运和通过电压门控通道的钙通量是表达氯化钠依赖性肾素释放所需的两种机制。确定这两种关键膜蛋白在肾素控制途径中的细胞定位需要进一步研究。
