Awazu M, Kon V, Harris R C, Imada T, Inagami T, Ichikawa I
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Am J Physiol. 1991 Jul;261(1 Pt 2):F29-35. doi: 10.1152/ajprenal.1991.261.1.F29.
We examined characteristics of atrial natriuretic peptide (ANP) receptors in glomeruli isolated from subacutely (3-5 days) denervated (DNX) and contralateral nondenervated (non-DNX) kidneys of normal rats (NL) and rats subjected to water deprivation for 48 h (WD). Total ANP receptor density in DNX kidneys of WD rats, measured by competitive inhibition binding between 125I-labeled ANP and ANP, was twofold higher than non-DNX kidneys (726 +/- 96 vs. 384 +/- 32 fmol/mg protein, P less than 0.05). Equilibrium association constant (Ka) was not significantly different (2.33 +/- 0.43 vs. 3.34 +/- 0.78 x 10(9) M-1). In NL rats, there was no difference in ANP receptor density between DNX and non-DNX kidneys (244 +/- 20 and 264 +/- 16 fmol/mg protein). Production of guanosine 3',5'-cyclic monophosphate (cGMP), a putative second messenger of ANP, in response to ANP (10(-7) M) in glomeruli isolated from DNX was significantly larger than non-DNX kidneys of WD rats. To determine whether these changes in ANP receptors have functional consequences in vivo, glomerular capillary ultrafiltration coefficient (Kf) was assessed by micropuncture technique in WD Munich-Wistar rats. In DNX kidneys, ANP infusion (4 micrograms.kg-1.h-1) significantly increased whole kidney glomerular filtration rate (GFR) and single-nephron (SN) GFR (0.64 +/- 0.06 to 0.89 +/- 0.17 ml/min and 25 +/- 2 to 33 +/- 2 nl/min, respectively; n = 7) and Kf (1.26 +/- 0.29 to 2.18 +/- 0.41 nl.min-1.mmHg-1).(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了从正常大鼠(NL)以及禁水48小时的大鼠(WD)亚急性(3 - 5天)去神经支配(DNX)肾脏和对侧未去神经支配(非DNX)肾脏分离出的肾小球中利钠肽(ANP)受体的特性。通过125I标记的ANP与ANP之间的竞争性抑制结合测定,WD大鼠DNX肾脏中的总ANP受体密度比非DNX肾脏高两倍(726±96对384±32 fmol/mg蛋白,P<0.05)。平衡缔合常数(Ka)无显著差异(2.33±0.43对3.34±0.78×10(9) M-1)。在NL大鼠中,DNX和非DNX肾脏之间的ANP受体密度无差异(244±20和264±16 fmol/mg蛋白)。从DNX分离出的肾小球中,对ANP(10(-7) M)产生的鸟苷3',5'-环磷酸(cGMP),一种假定的ANP第二信使,显著大于WD大鼠的非DNX肾脏。为了确定ANP受体的这些变化在体内是否具有功能后果,通过微穿刺技术在WD慕尼黑-威斯塔大鼠中评估了肾小球毛细血管超滤系数(Kf)。在DNX肾脏中,输注ANP(4微克·千克-1·小时-1)显著增加了全肾肾小球滤过率(GFR)和单肾单位(SN)GFR(分别从0.64±0.06至0.89±0.17毫升/分钟和25±2至33±2纳升/分钟;n = 7)以及Kf(1.26±0.29至2.18±0.41纳升·分钟-1·毫米汞柱-1)。(摘要截断于250字)