Wang Tao, Kawabata Masahiko, Haneda Manabu, Takabatake Toshikazu
Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Hypertens Res. 2003 Jul;26(7):577-82. doi: 10.1291/hypres.26.577.
Uroguanylin is an endogenous peptide that stimulates cyclic guanosine monophosphate (cGMP) production via the activation of guanylate cyclase C (GC-C) in the intestine and kidney. A high salt diet, but not intravenous salt load, enhances the secretion of biologically active uroguanylin from the intestine and increases its concentration in plasma and urine. Our purpose is to clarify the effect of uroguanylin on renal microcirculation and the tubuloglomerular feedback (TGF) mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to orthograde loop perfusion at 40 nl/min with artificial tubular fluid (ATF). Reductions in EPFR induced by loop perfusion during intravenous infusion of uroguanylin at the rate of 10 and 50 nmol/kg/h were similar yet significantly less than that during the control period (33+/-3% and 35+/-3% vs. 47+/-3%, p<0.05). Intraluminal application of uroguanylin at 10(-7) and 10(-5) mol/l in ATF decreased EPFR by 40+/-3% and 33+/-7%, respectively, with the latter value being significantly less than the control (p<0.05). Intravenous infusion of uroguanylin did not significantly change whole kidney function. Administration of atrial natriuretic peptide (ANP), which activates GC-A and B, significantly suppressed TGF-mediated EPFR reduction either intravenously (10 nmol/kg/h) or intraluminally (10(-5) mol/l in ATF) (9+/-3% and 13+/-2% vs. 47+/-3% of the control, p<0.05). In conclusion, uroguanylin clearly suppresses TGF both through intravenous and intraluminal routes, although the effects on glomerular microcirculation and whole kidney function are far less than those of ANP.
尿鸟苷素是一种内源性肽，可通过激活肠道和肾脏中的鸟苷酸环化酶C（GC-C）来刺激环磷酸鸟苷（cGMP）的产生。高盐饮食而非静脉内盐负荷可增强肠道中生物活性尿鸟苷素的分泌，并增加其在血浆和尿液中的浓度。我们的目的是阐明尿鸟苷素对肾微循环和肾小管-肾小球反馈（TGF）机制的影响。在麻醉大鼠中进行了清除率和微穿刺实验。通过测量在以40 nl/min的速度用人工肾小管液（ATF）进行顺行髓袢灌注时早期近端流速（EPFR）的变化，评估浅表肾单位中的TGF反应性。在以10和50 nmol/kg/h的速率静脉输注尿鸟苷素期间，髓袢灌注引起的EPFR降低相似，但明显低于对照期（分别为33±3%和35±3%，而对照期为47±3%，p<0.05）。在ATF中以10⁻⁷和10⁻⁵ mol/l的浓度腔内应用尿鸟苷素分别使EPFR降低40±3%和33±7%，后者的值明显低于对照（p<0.05）。静脉输注尿鸟苷素未显著改变全肾功能。静脉内（10 nmol/kg/h）或腔内（ATF中10⁻⁵ mol/l）给予激活GC-A和B的心房利钠肽（ANP），均显著抑制TGF介导的EPFR降低（分别为对照值的9±3%和13±2%，而对照值为47±3%，p<0.05）。总之，尿鸟苷素通过静脉和腔内途径均能明显抑制TGF，尽管其对肾小球微循环和全肾功能的影响远小于ANP。
