Loria Analia, Reverte Virginia, Salazar Francisco, Saez Fara, Llinas M Teresa, Salazar F Javier
Department of Physiology, School of Medicine, University of Murcia, 30100 Murcia, Spain.
Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R695-700. doi: 10.1152/ajpregu.00191.2007. Epub 2007 May 9.
The aim was to evaluate whether blockade of ANG II effects during renal development modifies the renal response to an increment of plasma amino acid concentration. It was also examined in anesthetized rats whether the reduction of the renal ability to eliminate an acute volume expansion (VE), elicited by blockade of ANG II during renal development, is sex and/or age dependent. Newborn Sprague-Dawley rats were treated with vehicle or an AT(1)-receptor antagonist (ARA) during postnatal nephrogenesis. Amino acid infusion induced increments (P < 0.05) of glomerular filtration rate (31 +/- 6%) and renal plasma flow (26 +/- 5%) in male but not in female vehicle-treated rats. Natriuretic and diuretic responses to amino acid infusion were similar in male and female vehicle-treated rats. These renal hemodynamics and excretory responses to amino acid infusion were abolished in ARA-treated rats. Renal responses to VE were evaluated at 3-4 and 9-10 mo of age in vehicle and ARA-treated rats. VE-induced natriuresis and diuresis were reduced by more than 38% (P < 0.05) in 3- to 4-mo-old male and female ARA-treated rats. An age-dependent reduction (P < 0.05) in the renal ability to eliminate VE was found in male but not in female rats treated with ARA. Our results demonstrate that the renal effects induced by an increment in amino acids are abolished when ANG II effects have been reduced during nephrogenesis. In addition, this reduction of ANG II effects elicits an impairment of the renal ability to eliminate an acute VE in males and females, which is aggravated by age only in male rats.
目的是评估在肾脏发育过程中阻断血管紧张素II(ANG II)的作用是否会改变肾脏对血浆氨基酸浓度升高的反应。同时,还在麻醉大鼠中研究了在肾脏发育过程中因阻断ANG II而导致的肾脏消除急性容量扩张(VE)能力的降低是否与性别和/或年龄有关。新生的Sprague-Dawley大鼠在出生后肾发生期间接受载体或AT(1)受体拮抗剂(ARA)治疗。氨基酸输注在雄性但不在雌性载体治疗的大鼠中诱导了肾小球滤过率(31±6%)和肾血浆流量(26±5%)的增加(P<0.05)。雄性和雌性载体治疗的大鼠对氨基酸输注的利钠和利尿反应相似。这些对氨基酸输注的肾脏血流动力学和排泄反应在ARA治疗的大鼠中被消除。在3-4个月和9-10个月龄时评估了载体和ARA治疗的大鼠对VE的肾脏反应。在3至4个月龄的雄性和雌性ARA治疗的大鼠中,VE诱导的利钠和利尿减少了超过38%(P<0.05)。在接受ARA治疗的雄性大鼠中发现了肾脏消除VE能力的年龄依赖性降低(P<0.05),而在雌性大鼠中未发现。我们的结果表明,当在肾发生期间ANG II的作用降低时,氨基酸增加所诱导的肾脏作用被消除。此外,ANG II作用的这种降低在雄性和雌性中引发了肾脏消除急性VE能力的损害,这种损害仅在雄性大鼠中随年龄加剧。