Watts S W, Harris B
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Gen Pharmacol. 1999 Dec;33(6):439-47. doi: 10.1016/s0306-3623(99)00040-3.
This study tests the hypothesis that the functional upregulation of the arterial 5-hydroxytryptamine (5-HT)2B receptor in arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats depends on the development of high blood pressure. Wistar-Furth and Wistar rats were given sham or DOCA-salt treatment (200 mg/kg DOCA, SC; 1.0% NaCl and 0.2% KCI in drinking water). Systolic blood pressures (4 week; mm Hg) were: Wistar Sham (120+/-3), Wistar DOCA (176+/-6), Wistar-Furth Sham (112+/-3) and Wistar-Furth DOCA (136+/-4). Isolated mesenteric arteries from Wistar DOCA and Wistar-Furth DOCA rats displayed a three- to fivefold leftward shift in contraction to 5-HT that was insensitive to blockade by the 5-HT2A receptor antagonist ketanserin (10 nM) and a significantly increased maximal contraction to the 5-HT2B receptor agonist BW723C86 [Wistar DOCA = 90+/-17% phenylephrine contraction; Wistar Sham = 1+/-1%; Wistar-Furth DOCA = 33+/-8%; Wistar-Furth Sham = 0%]. Arteries from Sprague-Dawley rats receiving salt or DOCA alone displayed similar systolic blood pressures (151+/-11 mm Hg and 144+/-5 mm Hg, respectively), but only tissues from rats receiving DOCA displayed an increased contraction to BW723C86 (DOCA alone = 60.7+/-16% vs. sham = 13+/-5.3%). These data suggest that upregulation of the arterial 5-HT2B receptor is largely independent of an increase in blood pressure.
醋酸脱氧皮质酮（DOCA）-盐性高血压大鼠动脉中5-羟色胺（5-HT）2B受体的功能上调取决于高血压的发展。对Wistar-Furth大鼠和Wistar大鼠进行假手术或DOCA-盐处理（皮下注射200mg/kg DOCA；饮用水中含1.0%NaCl和0.2%KCl）。4周时的收缩压（mmHg）分别为：Wistar假手术组（120±3）、Wistar DOCA组（176±6）、Wistar-Furth假手术组（112±3）和Wistar-Furth DOCA组（136±4）。来自Wistar DOCA大鼠和Wistar-Furth DOCA大鼠的离体肠系膜动脉对5-HT的收缩反应向左移位了三到五倍，这对5-HT2A受体拮抗剂酮色林（10nM）的阻断不敏感，并且对5-HT2B受体激动剂BW723C86的最大收缩反应显著增加[Wistar DOCA = 90±17%去氧肾上腺素收缩；Wistar假手术组 = 1±1%；Wistar-Furth DOCA组 = 33±8%；Wistar-Furth假手术组 = 0%]。单独接受盐或DOCA的Sprague-Dawley大鼠的动脉显示出相似的收缩压（分别为151±11mmHg和144±5mmHg），但只有接受DOCA的大鼠组织对BW723C86的收缩反应增加（单独DOCA组 = 60.7±16%，假手术组 = 13±5.3%）。这些数据表明，动脉5-HT2B受体的上调在很大程度上独立于血压升高。
