Local renal medullary L-NAME infusion enhances the effect of long-term angiotensin II treatment.
Local renal medullary L-NAME infusion enhances the effect of long-term angiotensin II treatment.
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局部肾髓质 L-NAME 输注可增强长期血管紧张素 II 治疗的效果。
DOI：
10.1161/01.hyp.33.1.440
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
CowleyJr,AW
中科院分区：
文献类型：
--
作者：
SzentiványiJr,M;Maeda,CY;CowleyJr,AW
我们假设在大鼠中产生高血压所需的相对高剂量的血管紧张素（Ang） II与刺激肾髓质一氧化氮的产生有关，这反过来又钝化了髓质血流量的减少和高血压的发展。在连续输注ng -硝基精氨酸甲酯（L-NAME）和不输注ng -硝基精氨酸甲酯（L-NAME）的情况下，向未切除的Sprague-Dawley大鼠输注Ang II（5天，剂量为3 ng·kg−1·min−1IV）。采用植入式光纤和激光多普勒血流仪测定肾皮质和髓质血流。在没有髓质一氧化氮合酶抑制的情况下，Ang II不改变皮质或髓质血流量或平均动脉压。L-NAME的阈值剂量（75 μg·kg−1·h−1）不会对髓质血流和平均动脉压产生显著的短期或长期变化。在髓质一氧化氮合酶活性钝化的大鼠中，静脉注射Ang II导致髓质血流量减少30%（从1.3降至0.9±0.2V），并在5天内使平均动脉压升高约20 mm Hg。在开始静脉注射Ang II后的70分钟内，髓质血流量立即减少，皮质血流量和平均动脉压没有变化。我们得出的结论是，大鼠对循环中II型一氧化氮的长期升高相对不敏感是由于一氧化氮系统，特别是在肾髓质内的强大的反调节作用。这些结果为生物体如何保护自己免受Ang II的高血压影响提供了新的见解。
—We hypothesized that the relatively high doses of angiotensin (Ang) II required to produce hypertension in rats were related to stimulation of renal medullary nitric oxide production, which in turn blunted reductions in medullary blood flow and the development of hypertension. Ang II was infused (5 days at 3 ng · kg−1· min−1IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of a continuous medullary interstitialNG-nitro-l-arginine methyl ester (L-NAME) infusion. Renal cortical and medullary blood flows were determined with the use of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of medullary nitric oxide synthase inhibition did not change cortical or medullary blood flow or mean arterial pressure. A threshold dose of L-NAME was determined (75 μg · kg−1· h−1) that did not produce significant short- or long-term changes in medullary blood flow and mean arterial pressure. In rats with blunted medullary nitric oxide synthase activity, Ang II infused intravenously resulted in a 30% reduction in medullary blood flow (from 1.3 to 0.9±0.2V) and ≈20 mm Hg increase in mean arterial pressure with Ang II infusion over 5 days. During 70 minutes after the start of intravenous Ang II, there was an immediate reduction in medullary blood flow, with no changes in cortical blood flow or mean arterial pressure. We conclude that the relative insensitivity of rats to long-term elevations of circulating Ang II is due to the potent counterregulatory actions of the nitric oxide system, specifically within the renal medulla. The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II.