Solhaug M J, Wallace M R, Granger J P
Department of Pediatrics, Eastern Virginia Medical School, Norfolk 23507, USA.
Pediatr Res. 1996 Mar;39(3):527-33. doi: 10.1203/00006450-199603000-00023.
We have previously shown that nitric oxide (NO) is a more important intrarenal vasodilator in the developing animal compared with the adult. The interaction between NO and the renin angiotensin system in the developing kidney is not known. The purpose of this study was to determine the role of NO and angiotensin II in the regulation of developing renal function. We examined the effects of the inhibition of intrarenal NO synthesis with N-nitro-L-arginine methyl ester (L-NAME), 3 micro g/kg/min, intrarenally, administered after intrarenal infusion of either saline or an angiotensin II AT1 receptor antagonist [ATX (A-81988), 0.4 micro g/kg/min] in piglets, age 3 wk, and adult pigs. The developing piglet demonstrated significantly greater renal responses to L-NAME alone. Intrarenal NO synthesis inhibition after saline preinfusion decreased renal blood flow (RBF) in the piglet 29% compared with the adult pig 9%, but only in the piglet decreased GFR 31%, and increased plasma renin activity 57%. Intrarenal infusion of ATX significantly increased RBF in the piglet, 23%, although not altering RBF in the adult. The renal responses to L-NAME were significantly attenuated by ATX preinfusion in both age groups. After ATX pretreatment, L-NAME in piglets decreased RBF 14%, and abolished the change in GFR, whereas in adult pigs decreased RBF only 5%.
我们之前已经表明,与成年动物相比,一氧化氮(NO)在发育中的动物体内是一种更重要的肾内血管舒张剂。发育中的肾脏中NO与肾素 - 血管紧张素系统之间的相互作用尚不清楚。本研究的目的是确定NO和血管紧张素II在发育中的肾功能调节中的作用。我们检查了用N - 硝基 - L - 精氨酸甲酯(L - NAME),3μg/kg/min,肾内给药抑制肾内NO合成的效果,在3周龄仔猪和成年猪肾内输注生理盐水或血管紧张素II AT1受体拮抗剂[ATX(A - 81988),0.4μg/kg/min]后进行。发育中的仔猪对单独使用L - NAME表现出明显更大的肾脏反应。与成年猪9%相比,生理盐水预输注后肾内NO合成抑制使仔猪肾血流量(RBF)降低29%,但仅在仔猪中肾小球滤过率(GFR)降低31%,血浆肾素活性增加57%。肾内输注ATX使仔猪RBF显著增加23%,尽管对成年猪的RBF没有影响。在两个年龄组中,ATX预输注均显著减弱了对L - NAME的肾脏反应。ATX预处理后,仔猪中L - NAME使RBF降低14%,并消除了GFR的变化,而成年猪中RBF仅降低5%。
1)血管紧张素II在发育中的肾脏中可能是一种更重要血管收缩剂,2)NO通过调节肾素 - 血管紧张素系统在发育中的肾脏中是一种更重要的肾功能调节剂。