Simeoni U, Zhu B, Muller C, Judes C, Massfelder T, Geisert J, Helwig J J
Laboratoire de Pharmacologie Physiologie Réno-vasculaire (CJF INSERM 9409), Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Pediatr Res. 1997 Oct;42(4):550-5. doi: 10.1203/00006450-199710000-00022.
Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.
对出生后发育中的家兔的离体灌注肾（IPK）进行了研究，以探讨：1）出生时高肾血管阻力（RVR）是否涉及肾脏内在机制；2）一氧化氮（NO）释放是否参与肾血管张力的调节；3）NO是否调节外源性血管紧张素II（AII）诱导的血管收缩。从1周龄（肾发生期）、3周龄（肾发生后）和6周龄家兔分离的肾脏在10(-5) M吲哚美辛存在下进行灌注。RVR随年龄从1周时的12.7±0.6降至6周时的10.1±0.5 mmHg min g mL-1。Nω-硝基-L-精氨酸甲酯（L-NAME，10(-4) M）在1、3和6周时使RVR同等程度增加约30%。10(-8) M AII诱导的血管收缩使基础压力从1周时的28%增加到6周时的78%，并被L-NAME增强约100%。相反，10(-10) M AII诱导的血管收缩从1周时的8%降至6周时的0%，并在1和3周时被L-NAME增强约250%。我们得出结论，在出生后发育过程中：1）在没有AII和肾外影响的情况下，IPK中的RVR降低，表明出生时的高RVR涉及内在机制；2）L-精氨酸/NO调节发育中IPK的基础张力；3）在出生后早期阶段，肾脏对外源性AII的血管收缩反应受到NO的缓冲，并遵循AII浓度依赖性发育模式。肾发生完成后消失的特定新生儿高亲和力AII/NO相互作用先于低亲和力AII/NO相互作用，后者随着年龄增长逐渐增加。这些发现支持AII-NO相互作用在发育中的肾脏血流动力学控制中具有特定作用。
