Intra-arterial Instillation of a Nociceptive Agent Modulates Cardiorespiratory Parameters Involving 5-HT3 and TRPV1 Receptors in Anesthetized Rats.

Sanjeev K Singh, M S Muthu, Ravindran Revand, Maloy B Mandal
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Abstract

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system.

Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats.

Materials and methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 μM) in the absence or presence of antagonists.

Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin- induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 μg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly.

Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

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麻醉大鼠动脉内灌注伤害性药物调节5-HT3和TRPV1受体的心肺参数
背景:长期以来,关于外周血管在心肺系统调节中的作用一直是一个讨论的问题。目的:研究氨基甲酸乙酯麻醉大鼠动脉灌注缓激肽后血管周围神经5-HT3和TRPV1受体对CVR反射的作用。材料和方法:股动脉逆行插管,采用双口24G插管,灌注生理盐水/激动剂/拮抗剂,记录血压。在没有或存在拮抗剂的情况下,给药1 μM后30 min记录血压、呼吸和心电图。结果:滴注缓激肽可产生瞬时低血压(40%)、心搏缓慢(17%)、呼吸急促(45%)和过度通气(96%)反应,潜伏期较短(5-8 s),有利于神经机制产生反应。在利多卡因(2%)预处理的动物中,缓激肽引起的低血压(10%)、心动过缓(1.7%)、呼吸急促(13%)和过度通气(13%)的反应显著减弱。用昂丹司琼(100 μg/kg)、5- ht3拮抗剂预处理可显著减弱降压(10%)、心动过缓(1.7%)、呼吸急促(11%)和过度通气(11%)的反应。用辣椒素(1 mg/kg)、瞬时受体电位香草素1-拮抗剂预处理可显著阻断降压(5%)、心动过缓(1.2%)、呼吸急促(6%)和过度通气(6%)的反应。结论:综上所述,麻醉大鼠血管周围感觉神经末梢TRPV1和5-HT3受体相关的CVR参数在动脉局部段存在时可引起血管感觉反射反应。
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来源期刊
Cardiovascular and Hematological Disorders - Drug Targets
Cardiovascular and Hematological Disorders - Drug Targets Medicine-Cardiology and Cardiovascular Medicine
CiteScore
1.90
自引率
0.00%
发文量
36
期刊介绍: Cardiovascular & Hematological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in cardiovascular and hematological disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cardiovascular and hematological disorders. As the discovery, identification, characterization and validation of novel human drug targets for cardiovascular and hematological drug discovery continues to grow.
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