Activation of the 5-HT(7) receptor but not nitric oxide synthase is necessary for chronic 5-hydroxytryptamine-induced hypotension.
Activation of the 5-HT(7) receptor but not nitric oxide synthase is necessary for chronic 5-hydroxytryptamine-induced hypotension.
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DOI：
10.1113/ep088919
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发表时间：
2020-12
影响因子：
2.7
通讯作者：
Watts SW
中科院分区：
文献类型：
--
作者：
Seitz BM;Fink GD;Watts SW
小剂量5-羟色胺（5-HT）输注大鼠可引起急性和慢性动脉血压下降。5-HT7受体亚型在观察到的低血压中起关键作用。急性（分钟至小时）5-HT输注对no没有抑制作用，但慢性条件下的5-HT抑制反应表明no的产生可能至关重要。我们测试了NO对5-HT的慢性而非急性抑制反应的假设。我们比较了NO和5-HT7受体在同一动物急性和慢性5-HT诱导的低血压中的作用。在生理盐水或5-羟色胺（25 μg/kg/min，渗透泵）输注5 d及停止输注2 d时，采用无线遥测法测量清醒大鼠的平均动脉压（MAP）和心率（HR）。为了量化NO和5- ht7受体对5- ht诱导的低血压的作用，在慢性输注1、3和5- ht泵停用后1天给予一氧化氮合酶（NOS）抑制剂L-NAME或选择性5- ht7受体拮抗剂SB267790。在没有或存在5-HT输注的情况下，L-NAME引起相同程度的升压反应。相反，在没有5-HT输注的情况下，SB269970不影响MAP，并在每个时间点逆转5-HT诱导的抑制反应。我们的研究结果表明，急性和慢性5-HT诱导的低血压不需要NOS激活，但需要5-HT7受体的持续激活。
Low dose infusion of 5-hydroxytryptamine (5-HT) to rats causes both an acute and chronic fall in arterial blood pressure. The 5-HT7 receptor subtype plays a critical part in the observed hypotension. Acute (minutes to hours) 5-HT infusion shows no depressor role for NO, but 5-HT depressor responses under chronic conditions suggest that NO production may be critical. We test the hypothesis that NO contributes to the chronic, but not acute, depressor response to 5-HT. We compared the role of NO and 5-HT7 receptors in 5-HT induced hypotension under acute and chronic conditions in the same animal. Mean arterial pressure (MAP) and heart rate (HR) were measured via radiotelemetry in conscious rats during 5 days of saline or 5-HT (25 μg/kg/min; osmotic pump) infusion and for two days after infusion was stopped. To quantify the contributions of NO and the 5-HT7 receptor to 5-HT-induced hypotension, the nitric oxide synthase (NOS) inhibitor L-NAME or the selective 5-HT7 receptor antagonist SB267790 were given at 1, 3 and 5 days of chronic infusion, and 1 day after 5-HT infusion pumps were removed. L-NAME caused a pressor response of the same magnitude in the absence or presence of 5-HT infusion. Conversely, SB269970 did not affect MAP in the absence of 5-HT infusion and reversed the 5-HT-induced depressor response at each time point. Our findings demonstrate that acute and chronic 5-HT induced hypotension does not require NOS activation but does require continued activation of the 5-HT7 receptor.