Morán Asunción, de Urbina Ana-Vega Ortiz, Martín María-Luisa, Rodríguez-Barbero Alicia, Román Luis San
Departamento de Fisiología y Farmacología, Laboratorio de Farmacognosia y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Spain.
Eur J Pharmacol. 2009 Oct 12;620(1-3):90-6. doi: 10.1016/j.ejphar.2009.08.026. Epub 2009 Aug 21.
We evaluated the renal vascular effects of serotonin in Nomega-Nitro-l-arginine-hypertensive rats (L-NAME, 30 mg/kg/day, administered over 21 days in drinking water), a model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous synthesis of nitric oxide (NO) and compared with those obtained in normotensive rats. Using several agonists and antagonists of 5-hydroxytryptamine (5-HT), we characterized the receptor subtypes involved in the contractile response to 5-HT in the in-situ autoperfused rat kidney. An intra-arterial (i.a.) bolus injection of 5-HT (0.00000125-0.1 microg/kg) increased renal perfusion pressure in a dose-dependent manner, but did not affect systemic blood pressure. The selective 5-HT(2) receptor agonist alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) caused a local vasoconstrictor effect in the autoperfused rat kidney. The selective 5-HT(2B) receptor agonist BW723C86, the non-selective 5-HT(2C) receptor agonist (1-(3-chlorophenyl) piperazine), m-CPP, the 5-HT(1) receptor agonist 5-carboxamidotryptamine (5-CT) and the selective 5-HT(3) receptor agonist (1-(m-chlorophenyl)-biguanide), m-CPBG, did not modify renal perfusion pressure. The vasoconstrictor effect elicited by alpha-methyl-5-HT was significantly decreased by the 5-HT(2) receptor antagonist ritanserin and the 5-HT(2A) receptor antagonist spiperone, but was not modified by pretreatment with the selective 5-HT(2B/2C) receptor antagonist (3,5-dihydro-5-methyl-N-3pyridinylbenzo[1,2.b:4,5-b']dipyrrole(1H)-carboxamide hydrochloride), SB206553. The results of protein expression analyses allow us to postulate that the 5-HT(2A) receptor protein 5HT-SRC is expressed in renal tissue and differentially expressed in the renal artery of hypertensive (L-NAME) rats. Our data suggest that the serotonergic vasoconstrictor response induced in the in-situ autoperfused hypertensive rat kidney would be mediated by local activation of the 5-HT(2A) receptor.
我们评估了血清素对N-ω-硝基-L-精氨酸高血压大鼠（L-NAME，30毫克/千克/天，通过饮用水给药21天）的肾血管作用，该模型是一种由于内源性一氧化氮（NO）合成长期受阻而导致肾小球毛细血管高血压和肾脏疾病的全身性高血压模型，并与正常血压大鼠的情况进行了比较。我们使用了几种5-羟色胺（5-HT）的激动剂和拮抗剂，对原位自体灌注大鼠肾脏中参与5-HT收缩反应的受体亚型进行了表征。动脉内（i.a.）推注5-HT（0.00000125 - 0.1微克/千克）以剂量依赖的方式增加了肾灌注压，但不影响全身血压。选择性5-HT(2)受体激动剂α-甲基-5-羟色胺（α-甲基-5-HT）在自体灌注大鼠肾脏中引起局部血管收缩作用。选择性5-HT(2B)受体激动剂BW723C86、非选择性5-HT(2C)受体激动剂（1-(3-氯苯基)哌嗪）、m-CPP、5-HT(1)受体激动剂5-羧酰胺色胺（5-CT）和选择性5-HT(3)受体激动剂（1-(间氯苯基)-双胍）、m-CPBG，均未改变肾灌注压。α-甲基-5-HT引起的血管收缩作用被5-HT(2)受体拮抗剂利坦色林和5-HT(2A)受体拮抗剂螺哌隆显著降低，但用选择性5-HT(2B/2C)受体拮抗剂（3,5-二氢-5-甲基-N-3-吡啶基苯并[1,2.b:4,5-b']二吡咯(1H)-羧酰胺盐酸盐）SB206553预处理并未改变这种作用。蛋白质表达分析结果使我们推测5-HT(2A)受体蛋白5HT-SRC在肾组织中表达，并在高血压（L-NAME）大鼠的肾动脉中差异表达。我们的数据表明，原位自体灌注高血压大鼠肾脏中诱导的血清素能血管收缩反应将由5-HT(2A)受体的局部激活介导。
