Zhang David X, Gauthier Kathryn M, Campbell William B
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
Endocrinology. 2004 Apr;145(4):1571-8. doi: 10.1210/en.2003-1448. Epub 2004 Jan 15.
The adrenal gland is highly vascularized with tightly regulated blood flow that is closely correlated with steroidogenesis. Mechanisms involved in the regulation of adrenal blood flow and vascular tone are largely unknown. The present study characterizes the contractile responses of isolated small cortical arteries from bovine adrenal glands. In endothelium-intact arteries, K(+), the thromboxane mimetic U46619, 5-hydroxytryptamine (5-HT), and endothelin-1 (ET-1) induced concentration-dependent contractions, whereas phenylephrine, norepinephrine, and ACTH were without effect. The EC(50)s for K(+), U46619, 5-HT, and ET-1 were 45 +/- 3 mm, 150 +/- 24 nm, 370 +/- 38 nm, and 2.8 +/- 0.8 nm, respectively. Contractions induced by U46619, 5-HT, and ET-1 were blocked by the thromboxane receptor antagonist SQ 29,548, the 5-HT(2A) receptor antagonist ketanserin, and the ET(A) receptor antagonist BQ 123, respectively. Removal of the endothelium caused a marked leftward shift of concentration responses to high K(+), U46619, 5-HT, and ET-1, and revealed contractile responses to phenylephrine and norepinephrine. In U46619-preconstricted arteries, BQ 123 converted ET-1-induced contractions to relaxations (maximal relaxation of 57 +/- 8%), which were subsequently blocked by the ET(B) receptor antagonist BQ 788. The ET(B)-mediated relaxations were endothelium dependent and inhibited by the nitric oxide synthase inhibitor N-nitro-l-arginine, the cytochrome P450 inhibitor SKF 525A, and high extracellular K(+), but not by the cyclooxygenase inhibitor indomethacin. These results demonstrate that small adrenal cortical arteries are highly responsive to various vasoconstrictor agents. The forceful contractile responses of these arterioles are consistent with their potential role in the regulation of adrenal blood flow.
肾上腺血管高度丰富，其血流受到严格调控，且与类固醇生成密切相关。肾上腺血流和血管张力调节所涉及的机制在很大程度上尚不清楚。本研究对来自牛肾上腺的分离小皮质动脉的收缩反应进行了表征。在内皮完整的动脉中，钾离子、血栓素类似物U46619、5-羟色胺（5-HT）和内皮素-1（ET-1）可诱导浓度依赖性收缩，而苯肾上腺素、去甲肾上腺素和促肾上腺皮质激素则无作用。钾离子、U46619、5-HT和ET-1的半数有效浓度（EC50）分别为45±3mmol/L、150±24nmol/L、370±38nmol/L和2.8±0.8nmol/L。U46619、5-HT和ET-1所诱导的收缩分别被血栓素受体拮抗剂SQ 29548、5-HT2A受体拮抗剂酮色林和ET A受体拮抗剂BQ 123阻断。去除内皮导致对高钾离子、U46619、5-HT和ET-1的浓度反应显著左移，并揭示了对苯肾上腺素和去甲肾上腺素的收缩反应。在U46619预收缩的动脉中，BQ 123将ET-1诱导的收缩转变为舒张（最大舒张为57±8%），随后被ET B受体拮抗剂BQ 788阻断。ET B介导的舒张依赖于内皮，并被一氧化氮合酶抑制剂N-硝基-L-精氨酸、细胞色素P450抑制剂SKF 525A和高细胞外钾离子抑制，但不被环氧化酶抑制剂吲哚美辛抑制。这些结果表明，肾上腺小皮质动脉对各种血管收缩剂高度敏感。这些小动脉强烈的收缩反应与其在肾上腺血流调节中的潜在作用一致。
