Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries.
Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries.
复制标题
组胺诱导牛肾上腺皮质小动脉松弛的机制。
DOI：
10.1152/ajpendo.00162.2005
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Campbell,WilliamB
中科院分区：
文献类型：
--
作者：
Zhang,DavidX;Gauthier,KathrynM;Campbell,WilliamB
肾上腺类固醇生成与肾上腺血流量增加密切相关。许多报告研究了肾上腺血流的调节在体内和灌注腺，但直到最近很少有研究已经进行了离体肾上腺动脉。本研究探讨了离体牛肾上腺皮质小动脉对组胺（一种内源性血管活性化合物）的血管舒张反应及其作用机制。在U-46619预收缩的动脉中，组胺（10−9-5 × 10− 6 M）引起浓度依赖性舒张。H1受体拮抗剂苯海拉明（10 μM）或美托咪胺（1 μM）可阻断这种舒张作用（最大舒张作用分别为18 ± 6%和22 ± 6%，对照组为55 ± 5%），但H2受体拮抗剂西咪替丁（10 μM）和H3受体拮抗剂硫代哌丁胺（1 μM）仅部分抑制这种舒张作用。组胺诱导的舒张作用也被一氧化氮合酶抑制剂或N-硝基-L-精氨酸（l-NA，30 μM;最大舒张为13 ± 7%）阻断，并被内皮细胞去除或l-NA联合环氧化酶抑制剂吲哚美辛（10 μM）消除。在肾上腺髓质小球（ZG）细胞的存在下，组胺并没有引起进一步的松弛相比，单独组胺。组胺（10−7-10− 5 M）浓度依赖性地增加肾上腺ZG细胞的醛固酮生成。化合物48/80（10 μg/ml），一种肥大细胞去极化剂，诱导显著的舒张（93 ± 0.6%），其被NA加吲哚美辛或内皮去除阻断，被H1、H2和H3受体拮抗剂的组合部分抑制，但不受肥大细胞稳定剂色甘酸钠（1 mM）的影响。这些结果表明，组胺引起肾上腺皮质小动脉的直接舒张，这在很大程度上是由内皮NO和肾上腺素通过H1受体介导的。组胺在肾上腺血管事件和类固醇分泌之间的潜在作用需要进一步研究。
Adrenal steroidogenesis is closely correlated with increases in adrenal blood flow. Many reports have studied the regulation of adrenal blood flow in vivo and in perfused glands, but until recently few studies have been conducted on isolated adrenal arteries. The present study examined vasomotor responses of isolated bovine small adrenal cortical arteries to histamine, an endogenous vasoactive compound, and its mechanism of action. In U-46619-precontracted arteries, histamine (10−9-5 × 10−6M) elicited concentration-dependent relaxations. The relaxations were blocked by the H1receptor antagonists diphenhydramine (10 μM) or mepyramine (1 μM) (maximal relaxations of 18 ± 6 and 22 ± 6%, respectively, vs. 55 ± 5% of control) but only partially inhibited by the H2receptor antagonist cimetidine (10 μM) and the H3receptor antagonist thioperamide (1 μM). Histamine-induced relaxations were also blocked by the nitric oxide synthase inhibitorN-nitro-l-arginine (l-NA, 30 μM; maximal relaxation of 13 ± 7%) and eliminated by endothelial removal orl-NA combined with the cyclooxgenase inhibitor indomethacin (10 μM). In the presence of adrenal zona glomerulosa (ZG) cells, histamine did not induce further relaxations compared with histamine alone. Histamine (10−7-10−5M) concentration-dependently increased aldosterone production by adrenal ZG cells. Compound 48/80 (10 μg/ml), a mast cell degranulator, induced significant relaxations (93 ± 0.6%), which were blocked byl-NA plus indomethacin or endothelium removal, partially inhibited by the combination of the H1, H2, and H3receptor antagonists, but not affected by the mast cell stabilizer sodium cromoglycate (1 mM). These results demonstrate that histamine causes direct relaxation of small adrenal cortical arteries, which is largely mediated by endothelial NO and prostaglandins via H1receptors. The potential role of histamine in linking adrenal vascular events and steroid secretion requires further investigation.