Verapamil abolishes the preglomerular response to ANG II during intrarenal nitric oxide synthesis inhibition.
Verapamil abolishes the preglomerular response to ANG II during intrarenal nitric oxide synthesis inhibition.
复制标题
维拉帕米在肾内一氧化氮合成抑制过程中消除了肾小球前对 ANG II 的反应。
DOI：
10.1152/ajpregu.1997.272.5.r1670
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Granger,JP
中科院分区：
文献类型：
--
作者：
Schnackenberg,CG;Granger,JP
我们最近报道，肾内一氧化氮（NO）的合成抑制夸大肾小球前血管收缩反应比肾小球后血管紧张素II（ANG II）的反应在狗。先前的研究表明，肾小球前血管收缩可能比肾小球后血管收缩更依赖于细胞外钙。本研究的目的是确定肾内NO合成抑制过程中血管紧张素II对肾小球前反应的增强是否通过电压门控钙通道发生。在三组具有停流肾的麻醉犬中，测定肾内输注ANG II（2.0 ng·kg-1·min-1）的肾血流动力学反应。肾动脉压伺服控制在80 +/-1 mmHg，肾小球滤过率为零。在溶剂处理的狗中，ANG II使肾血流量（RBF）降低29%，并使肾小球静水压力（Pg）增加2.7 +/-1.9 mmHg。肾小球后血管阻力增加了51%，而肾小球前阻力在ANG II反应中没有变化。在肾内注射NG-硝基-L-精氨酸甲酯（L-NAME; 5 μ g·kg-1·min-1）60分钟的狗中，ANG II使RBF降低36%，Pg降低4.4 +/-2.9 mmHg。与溶剂处理组相比，在L-NAME处理组中ANG II输注后，肾小球前阻力增加261%，肾小球后阻力增加48%。在预先肾内输注L-NAME和维拉帕米（50微克/分钟）60分钟的犬中，肾脏对ANG II的血流动力学反应与溶剂处理犬中的反应相似。ANG II使RBF降低25%，使Pg降低5.3 +/-1.2 mmHg。肾小球后阻力增加了51%，而肾小球前阻力在肾内NO合成和电压门控钙通道阻滞犬中对ANG II输注的反应不变。这些数据表明，肾小球前反应血管紧张素Ⅱ的条件下，减少NO合成的肾脏是依赖于电压门控钙通道。
We have recently reported that intrarenal nitric oxide (NO) synthesis inhibition exaggerates the preglomerular vasoconstrictor response more than the postglomerular response to angiotensin II (ANG II) in dogs. Previous studies have suggested that preglomerular vasoconstriction may be more dependent on extracellular calcium than postglomerular vasoconstriction. The purpose of this study is to determine whether the enhanced preglomerular response to ANG II during intrarenal NO synthesis inhibition occurs through voltage-gated calcium channels. In three groups of anesthetized dogs with stop-flow kidneys, the renal hemodynamic response to intrarenal ANG II infusion (2.0 ng.kg-1.min-1) was determined. Renal artery pressure was servo-controlled at 80 +/- 1 mmHg, and glomerular filtration rate was zero. In vehicle-treated dogs, ANG II decreased renal blood flow (RBF) by 29% and increased glomerular hydrostatic pressure (Pg) by 2.7 +/- 1.9 mmHg. Postglomerular vascular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II. In dogs pretreated with an intrarenal infusion of NG-nitro-L-arginine methyl ester (L-NAME; 5 micrograms.kg-1.min-1) for 60 min, ANG II decreased RBF by 36% and decreased Pg 4.4 +/- 2.9 mmHg. In contrast to the vehicle-treated group, preglomerular resistance increased by 261% and postglomerular resistance increased by 48% after ANG II infusion in the L-NAME-treated group. In dogs pretreated with an intrarenal infusion of L-NAME and verapamil (50 micrograms/min) for 60 min, the renal hemodynamic response to ANG II was similar to the response in the vehicle-treated dogs. ANG II decreased RBF by 25% and decreased Pg by 5.3 +/- 1.2 mmHg. Postglomerular resistance increased by 51%, whereas preglomerular resistance was unchanged in response to ANG II infusion in dogs with intrarenal NO synthesis and voltage-gated calcium channel blockade. These data indicate that the preglomerular response to ANG II under conditions of reduced NO synthesis within the kidney is dependent on voltage-gated calcium channels.