Watts Stephanie W
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Hypertension. 2002 Mar 1;39(3):825-9. doi: 10.1161/hy0302.104668.
Large arteries from hypertensive subjects are hyperresponsiveness to 5-hydroxytryptamine (5-HT). We tested the hypothesis that small arteries (225 micro ID) have a profile similar to conduit arteries, including signal transduction mechanisms and the 5-HT receptor subtype(s) mediating arterial contraction in normal and high blood pressure. Aorta and mesenteric arteries from Sprague-Dawley (232+/-6 micro ID), sham (229+/-7 micro ID; systolic blood pressure, 120+/-2 mm Hg), or deoxycorticosterone acetate (DOCA)-salt rats (255+/-11 micro ID, 192+/-8 mm Hg) were mounted in a wire-based myograph. In resistance arteries from Sprague-Dawley rats, the 5-HT2A receptor mediated contraction; agonists of the 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT2B receptor were inactive. The tyrosine kinase inhibitor genistein (5 micromol/L, 4.8-fold rightward shift), PD 098,059 (10 micromol/L, 3.2-fold shift), phospholipase C inhibitor NCDC (100 micromol/L), and nifedipine (50 nmol/L) reduced maximum 5-HT-induced contraction in small arteries (4.5% and 53% control, respectively). As in aorta, 5-HT had a decrease in threshold (100-fold lower), increase in potency (11.6-fold leftward shift), and increase in efficacy (140% sham response) in small arteries from DOCA-salt rats compared with sham. Unlike in aorta, 5-HT-induced contraction in DOCA-salt small arteries was shifted competitively by the 5-HT2A receptor antagonist ketanserin (-log K(B) [mol/L] for both sham and DOCA-salt, 9.25+/-0.1), and contraction to the 5-HT2B agonist BW723C86 was not observed. Thus, the 5-HT2A receptor remains the contractile receptor in hypertension in small arteries. Although similarities were observed for large and small arteries, differences under the condition of DOCA-salt hypertension exist that may determine serotonergic compounds effective in lowering blood pressure.
高血压患者的大动脉对5-羟色胺（5-HT）反应过度。我们验证了一个假设，即小动脉（内径225微米）具有与传导动脉相似的特征，包括信号转导机制以及在正常血压和高血压状态下介导动脉收缩的5-HT受体亚型。将来自斯普拉格-道利大鼠（内径232±6微米）、假手术大鼠（内径229±7微米；收缩压120±2毫米汞柱）或醋酸脱氧皮质酮（DOCA）-盐处理大鼠（内径255±11微米，192±8毫米汞柱）的主动脉和肠系膜动脉安装在基于线的肌动描记器上。在斯普拉格-道利大鼠的阻力动脉中，5-HT2A受体介导收缩；5-HT1B、5-HT1D、5-HT1F和5-HT2B受体激动剂无活性。酪氨酸激酶抑制剂染料木黄酮（5微摩尔/升，向右移位4.8倍）、PD 098,059（10微摩尔/升，移位3.2倍）、磷脂酶C抑制剂NCDC（100微摩尔/升）和硝苯地平（50纳摩尔/升）可降低小动脉中5-HT诱导的最大收缩（分别为对照的4.5%和53%）。与假手术组相比，在DOCA-盐处理大鼠的小动脉中，5-HT的阈值降低（低100倍）、效力增加（向左移位11.6倍）且效能增加（为假手术反应的140%），与主动脉情况相同。与主动脉不同的是，DOCA-盐处理的小动脉中5-HT诱导的收缩被5-HT2A受体拮抗剂酮色林竞争性移位（假手术组和DOCA-盐处理组的-log K(B) [摩尔/升]均为9.25±0.1），且未观察到对5-HT2B激动剂BW723C86的收缩反应。因此，5-HT2A受体仍是高血压状态下小动脉中的收缩受体。虽然在大动脉和小动脉中观察到了相似性，但在DOCA-盐高血压状态下存在差异，这可能决定了对降低血压有效的血清素类化合物。
