Tojo A, Tisher C C, Madsen K M
Division of Nephrology, Hypertension, and Transplantation, College of Medicine, University of Florida, Gainesville 32610.
Am J Physiol. 1994 Dec;267(6 Pt 2):F1045-51. doi: 10.1152/ajprenal.1994.267.6.F1045.
Angiotensin II (ANG II) plays an important role in the regulation of solute transport in the kidney, and its effect on proximal tubule sodium and fluid transport has been studied extensively. Although there is evidence that ANG II receptors are present also in the distal nephron and collecting duct, little is known about the physiological role of ANG II in these segments of the renal tubule. Preliminary studies in our laboratory suggest that ANG II may have both structural and functional effects on intercalated cells in the cortical collecting duct (CCD). Therefore, the present study examines the effect of ANG II on H(+)-adenosinetriphosphatase (H(+)-ATPase) and H(+)-K(+)-ATPase activity in individual CCD segments microdissected from collagenase-treated rat kidneys. The H(+)-ATPase was measured as bafilomycin-sensitive ATPase activity, and H(+)-K(+)-ATPase was measured as Sch-28080-sensitive ATPase activity, by a fluorometric microassay. Preincubation of CCD segments with ANG II, 10(-10)-10(-5) M, caused a dose-dependent decrease in H(+)-ATPase activity with maximum inhibition at 10(-8) M of ANG II. The inhibitory effect of ANG II was abolished when tubules were incubated with ANG II in the presence of 10(-6) M losartan, indicating that the inhibition was mediated via specific AT1 receptors. The AT2-receptor antagonist, PD-123319, had no effect on the ANG II-mediated inhibition of H(+)-ATPase activity. Preincubation of CCD segments with 10(-10) or 10(-7) M ANG II had no effect on H(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
血管紧张素II（ANG II）在肾脏溶质转运调节中起重要作用，其对近端小管钠和液体转运的影响已得到广泛研究。尽管有证据表明ANG II受体也存在于远端肾单位和集合管中，但对于ANG II在肾小管这些节段中的生理作用知之甚少。我们实验室的初步研究表明，ANG II可能对皮质集合管（CCD）中的闰细胞具有结构和功能上的影响。因此，本研究检测了ANG II对从经胶原酶处理的大鼠肾脏中显微解剖出的单个CCD节段中H⁺-腺苷三磷酸酶（H⁺-ATP酶）和H⁺-K⁺-ATP酶活性的影响。通过荧光微量测定法，将H⁺-ATP酶测定为巴弗洛霉素敏感的ATP酶活性，将H⁺-K⁺-ATP酶测定为Sch-28080敏感的ATP酶活性。用10⁻¹⁰ - 10⁻⁵ M的ANG II对CCD节段进行预孵育，导致H⁺-ATP酶活性呈剂量依赖性降低，在10⁻⁸ M的ANG II时抑制作用最大。当肾小管在10⁻⁶ M氯沙坦存在下与ANG II一起孵育时，ANG II的抑制作用被消除，表明该抑制作用是通过特异性AT1受体介导的。AT2受体拮抗剂PD-123,319对ANG II介导的H⁺-ATP酶活性抑制没有影响。用10⁻¹⁰或10⁻⁷ M的ANG II对CCD节段进行预孵育对H⁺-K⁺-ATP酶活性没有影响。（摘要截短至250字）
