Suzuki Y, Matsumura Y, Egi Y, Morimoto S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
J Pharmacol Exp Ther. 1992 Dec;263(3):956-63.
We examined the role of endogenous angiotensin II on renal noradrenergic neurotransmission in anesthetized dogs, using Losartan, a nonpeptide angiotensin II receptor (angiotensin subtype 1) antagonist. The renal nerve stimulation caused a frequency-dependent increase in renal norepinephrine secretion rate. The low frequency renal nerve stimulation (0.5-2.0 Hz) significantly decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. The high frequency renal nerve stimulation (2.5-5.0 Hz) produced a more potent antidiuresis and a renal vasoconstriction that resulted in reductions of renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of Losartan (10 and 100 micrograms/kg/min) did not affect the basal levels of norepinephrine secretion rate, although increased urine formation with some renal vasodilation were observed during infusion of the drug. The administration of Losartan had an inhibitory action on the decreased urine formation, renal vasoconstriction and enhanced norepinephrine secretion rate, in response to renal nerve stimulation. Based on these findings, we suggest that endogenous angiotensin II seems to regulate renal noradrenergic neurotransmission by facilitating norepinephrine release, through the prejunctional angiotensin subtype 1 receptor.
我们使用非肽类血管紧张素II受体（1型血管紧张素亚型）拮抗剂氯沙坦，研究了内源性血管紧张素II在麻醉犬肾去甲肾上腺素能神经传递中的作用。肾神经刺激导致肾去甲肾上腺素分泌率呈频率依赖性增加。低频肾神经刺激（0.5 - 2.0赫兹）显著降低尿量和尿钠排泄，而不影响肾血流动力学。高频肾神经刺激（2.5 - 5.0赫兹）产生更强的抗利尿作用和肾血管收缩，导致肾血流量和肾小球滤过率降低。肾内动脉输注氯沙坦（10和100微克/千克/分钟）不影响去甲肾上腺素分泌率的基础水平，尽管在输注药物期间观察到尿量增加并伴有一些肾血管舒张。氯沙坦给药对肾神经刺激引起的尿量减少、肾血管收缩和去甲肾上腺素分泌率增加具有抑制作用。基于这些发现，我们认为内源性血管紧张素II似乎通过作用于节前1型血管紧张素受体促进去甲肾上腺素释放，从而调节肾去甲肾上腺素能神经传递。
