Zhang David X, Gauthier Kathryn M, Campbell William B
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1058-63. doi: 10.1152/ajpendo.00162.2005. Epub 2005 Aug 2.
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 x 10(-6) M) elicited concentration-dependent relaxations. The relaxations were blocked by the H(1) receptor antagonists diphenhydramine (10 microM) or mepyramine (1 microM) (maximal relaxations of 18 +/- 6 and 22 +/- 6%, respectively, vs. 55 +/- 5% of control) but only partially inhibited by the H(2) receptor antagonist cimetidine (10 microM) and the H(3) receptor antagonist thioperamide (1 microM). Histamine-induced relaxations were also blocked by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 microM; maximal relaxation of 13 +/- 7%) and eliminated by endothelial removal or L-NA combined with the cyclooxgenase inhibitor indomethacin (10 microM). In the presence of adrenal zona glomerulosa (ZG) cells, histamine did not induce further relaxations compared with histamine alone. Histamine (10(-7)-10(-5) M) concentration-dependently increased aldosterone production by adrenal ZG cells. Compound 48/80 (10 microg/ml), a mast cell degranulator, induced significant relaxations (93 +/- 0.6%), which were blocked by L-NA plus indomethacin or endothelium removal, partially inhibited by the combination of the H(1), H(2), and H(3) receptor 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 H(1) receptors. The potential role of histamine in linking adrenal vascular events and steroid secretion requires further investigation.
肾上腺类固醇生成与肾上腺血流量增加密切相关。许多报告研究了体内和灌注腺体中肾上腺血流量的调节，但直到最近，对分离的肾上腺动脉的研究还很少。本研究检测了分离的牛小肾上腺皮质动脉对组胺（一种内源性血管活性化合物）的血管舒缩反应及其作用机制。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。这些舒张反应被H(1)受体拮抗剂苯海拉明（10μM）或美吡拉敏（1μM）阻断（最大舒张分别为18±6%和22±6%，而对照组为55±5%），但仅被H(2)受体拮抗剂西咪替丁（10μM）和H(3)受体拮抗剂硫代哌啶（1μM）部分抑制。组胺诱导的舒张也被一氧化氮合酶抑制剂N-硝基-L-精氨酸（L-NA，30μM；最大舒张为13±7%）阻断，并通过去除内皮或L-NA与环氧化酶抑制剂吲哚美辛（10μM）联合使用而消除。在存在肾上腺球状带（ZG）细胞的情况下，与单独使用组胺相比，组胺并未诱导进一步的舒张。组胺（10^(-7)-10^(-5)M）浓度依赖性地增加肾上腺ZG细胞的醛固酮分泌。化合物48/80（10μg/ml），一种肥大细胞脱颗粒剂，诱导显著舒张（93±0.6%），其被L-NA加吲哚美辛或去除内皮阻断，被H(1)、H(2)和H(3)受体拮抗剂联合部分抑制，但不受肥大细胞稳定剂色甘酸钠（1mM）影响。这些结果表明，组胺可引起小肾上腺皮质动脉的直接舒张，这在很大程度上是由内皮一氧化氮和前列腺素通过H(1)受体介导的。组胺在连接肾上腺血管事件和类固醇分泌中的潜在作用需要进一步研究。
