Angiotensin II dilates bovine adrenal cortical arterioles: Role of endothelial nitric oxide
Angiotensin II dilates bovine adrenal cortical arterioles: Role of endothelial nitric oxide
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DOI：
10.1210/en.2005-0129
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
Campbell, WB
中科院分区：
文献类型：
--
作者：
Gauthier, KM;Zhang, DX;Campbell, WB
肾上腺类固醇生成受体液和神经元因素以及血流的调节。血管紧张素 II (AII) 刺激肾上腺皮质醛固酮和皮质醇的产生以及髓质儿茶酚胺的释放。然而，AII 对肾上腺血管张力的调节尚未得到表征。我们研究了 AII 对插管牛肾上腺皮质动脉直径的影响。用U46619使皮质动脉(平均内径＝230μm)收缩，并测量对AII(10(-13)至10(-8)mol/升)的浓度-直径反应。在内皮完整的动脉中，AII 在低浓度下诱导扩张（最大扩张 = 25 +/- 6%，在 10(-10) 摩尔/升），在高浓度下诱导收缩（最大收缩 = 25 +/- 18%，在 10(-8) 摩尔/升）。所有收缩均被1型血管紧张素(AT1)受体拮抗剂氯沙坦(10(-6)mol/L)阻断。所有扩张均被氯沙坦增强（最大扩张 = 48 +/- 8%），通过内皮细胞去除或 N-硝基-L-精氨酸（L-NA，3 x 10(-5) mol/L）消除，并被血管紧张素 2 型（AT(2)）受体拮抗剂 PD123319（10(-6) mol/L，最大扩张 = 18 +/- 抑制） 4%）。在离体皮质动脉的 4,5-二氨基荧光素二乙酸一氧化氮 (NO) 测定中，AII 刺激 NO 产生，但通过 PD123319、L-NA 或去除内皮细胞可消除 NO 产生。动脉匀浆和内皮细胞和肾小球带细胞裂解物的蛋白质免疫印迹显示，所有三个中分别对应于 AT1 和 AT2 受体的 48 kD 和 50 kD 条带，以及对应于内皮细胞和动脉中的内皮 NO 合酶的 140 kD 条带。我们的结果表明，AII 通过内皮细胞 AT2 受体激活和 NO 释放以及 AT1 受体依赖性收缩来刺激肾上腺皮质动脉扩张。
Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II ( AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries ( average internal diameter = 230 mu m) were constricted with U46619 and concentration-diameter responses to AII (10(-13) to 10(-8) mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations ( maximum dilation = 25 +/- 6% at 10(-10) mol/liter) and constrictions at high concentrations ( maximum constriction = 25 +/- 18% at 10(-8) mol/ liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10(-6) mol/liter). AII dilations were enhanced by losartan ( maximal dilation = 48 +/- 8%), abolished by endothelial cell removal or N-nitro-L-arginine (L-NA, 3 x 10(-5) mol/liter) and inhibited by the angiotensin type 2 (AT(2)) receptor antagonist, PD123319 (10(-6) mol/liter, maximal dilation = 18 +/- 4%). In a 4,5-diaminofluorescein diacetate nitric oxide ( NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.