Sanjeev K Singh, M S Muthu, Ravindran Revand, Maloy B Mandal
{"title":"Intra-arterial Instillation of a Nociceptive Agent Modulates Cardiorespiratory Parameters Involving 5-HT3 and TRPV1 Receptors in Anesthetized Rats.","authors":"Sanjeev K Singh, M S Muthu, Ravindran Revand, Maloy B Mandal","doi":"10.2174/1871529X21666210408101442","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system.</p><p><strong>Objective: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9543,"journal":{"name":"Cardiovascular and Hematological Disorders - Drug Targets","volume":"21 1","pages":"46-54"},"PeriodicalIF":0.0000,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular and Hematological Disorders - Drug Targets","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1871529X21666210408101442","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
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.
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.