Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain; Research Institute of Salamanca (IBSAL), Paseo San Vicente 58-182, 37007, Salamanca, Spain.
Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain.
J Pharmacol Sci. 2021 Sep;147(1):48-57. doi: 10.1016/j.jphs.2021.05.008. Epub 2021 May 23.
Given the interconnection between depressive and cardiovascular disorders, we investigated whether antidepressant treatment (fluoxetine) modifies the serotonergic influence on rat vascular noradrenergic outflow. Twelve-week-old male Wistar rats received fluoxetine treatment (10 mg/kg/day; p.o.) for 14 days; then, they were pithed and prepared for sympathetic stimulation. Vasopressor responses were obtained by electrical stimulation of the sympathetic outflow (0.1, 0.5, 1, and 5 Hz) or i.v. noradrenaline (NA; 0.01, 0.05, 0.1, and 0.5 μg/kg). In fluoxetine-treated group, the electrical-induced vasoconstrictions were lower compared to non-treated rats. Intravenous infusion of 5-HT (10 μg/kg/min) inhibited the sympathetically-induced vasoconstrictions. Only 5-CT, 8-OH-DPAT and L-694,247 (5-HT, 5-HT and 5-HT agonists, respectively) mimicked 5-HT-induced inhibition, while α-methyl-5-HT (5-HT agonist) increased the vasopressor responses. The inhibitory effect of 5-HT was: a) no modified by SB269970 (5-HT antagonist); b) abolished by WAY-100,635 (5-HT antagonist) plus LY310762 (5-HT antagonist); and c) potentiated by ritanserin (5-HT receptor antagonist). The vasoconstrictions induced by exogenous NA were not modified by 5-CT but were increased by α-methyl-5-HT. Our results suggest that fluoxetine treatment decreases NA release at vascular level and changes 5-HT modulation on rat vascular noradrenergic neurotransmission, inducing sympatho-inhibition via prejunctional 5-HT receptors, and sympatho-potentiation via pre and/or postjunctional 5-HT receptors.
鉴于抑郁和心血管疾病之间的相互关系，我们研究了抗抑郁治疗（氟西汀）是否会改变 5-羟色胺对大鼠血管去甲肾上腺素流出的影响。12 周龄雄性 Wistar 大鼠接受氟西汀治疗（10mg/kg/天；口服）14 天；然后，它们被开颅并准备进行交感神经刺激。通过刺激交感神经流出（0.1、0.5、1 和 5Hz）或静脉内给予去甲肾上腺素（NA；0.01、0.05、0.1 和 0.5μg/kg）获得加压反应。与未治疗的大鼠相比，氟西汀治疗组的电刺激引起的血管收缩较低。静脉内输注 5-HT（10μg/kg/min）抑制了交感神经引起的血管收缩。只有 5-CT、8-OH-DPAT 和 L-694,247（5-HT、5-HT 和 5-HT 激动剂，分别）模拟 5-HT 诱导的抑制，而α-甲基-5-HT（5-HT 激动剂）增加了升压反应。5-HT 的抑制作用：a）不被 SB269970（5-HT 拮抗剂）改变；b）被 WAY-100,635（5-HT 拮抗剂）加 LY310762（5-HT 拮抗剂）消除；c）被 ritanserin（5-HT 受体拮抗剂）增强。外源性 NA 引起的血管收缩不受 5-CT 影响，但受α-甲基-5-HT 影响增加。我们的结果表明，氟西汀治疗降低了血管水平的 NA 释放，并改变了 5-HT 对大鼠血管去甲肾上腺素神经传递的调节，通过前突触 5-HT 受体诱导交感抑制，并通过前和/或后突触 5-HT 受体诱导交感兴奋。
