Hilchey S, Quilley J, Bell-Quilley C
Department of Pharmacology, New York Medical College, Valhalla, N.Y., USA.
Pharmacology. 1998 Oct;57(4):196-205. doi: 10.1159/000028242.
Angiotensin II (AII) is a potent vasoconstrictor which, at physiological plasma concentrations, produces antinatriuresis, whereas high intrarenal concentrations cause natriuresis and diuresis. We examined the effects of a selective AT1 receptor antagonist, losartan, and a nonselective AT receptor antagonist, Sar1Thr8AII, on the response to infusion of AII in the isolated rat kidney perfused at constant pressure with a recirculating modified Krebs-Henseleit buffer. AII increased renal vascular resistance (RVR), glomerular filtration rate (GFR) and urinary volume (UV) and sodium excretion (UNaV) without changing the fractional excretion of water or electrolytes. Thus, changes in GFR can account for the natriuresis/diuresis. Both AII receptor antagonists prevented the increase in RVR. However, losartan was without effect on angiotensin-induced increases in GFR, UV or UNaV, whereas Sar1Thr8 AII also prevented the increases in GFR, UV and UNaV. The angiotensin receptor mediating the increase in GFR can be dissociated from that mediating the increase in RVR, providing functional evidence of angiotensin receptor subtypes in the rat kidney.
血管紧张素II（AII）是一种强效血管收缩剂，在生理血浆浓度下可产生抗利尿作用，而高肾内浓度则会导致利尿和利钠。我们研究了选择性AT1受体拮抗剂氯沙坦和非选择性AT受体拮抗剂Sar1Thr8AII对在恒压下用循环改良Krebs-Henseleit缓冲液灌注的离体大鼠肾脏中输注AII反应的影响。AII增加了肾血管阻力（RVR）、肾小球滤过率（GFR）和尿量（UV）以及钠排泄（UNaV），而未改变水或电解质的排泄分数。因此，GFR的变化可解释利尿/利钠现象。两种AII受体拮抗剂均能阻止RVR的增加。然而，氯沙坦对血管紧张素诱导的GFR、UV或UNaV增加没有影响，而Sar1Thr8AII也能阻止GFR、UV和UNaV的增加。介导GFR增加的血管紧张素受体可与介导RVR增加的受体分离，这为大鼠肾脏中血管紧张素受体亚型提供了功能证据。
