Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery

Background: Nitric oxide (NO) is a colorless and odorless toxic gas and a short-acting physiological vasodilator. NO is produced by nitric oxide synthase (NOS). NOS has three isoforms, including endothelium NOS, neuronal NOS, and inducible NOS (iNOS). Many NOS inhibitors are analogs for the amino ac...

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Main Author: Xian-He Shyanher Wang
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2023-01-01
Series:Tungs’ Medical Journal
Subjects:
Online Access:https://journals.lww.com/TMJ/Pages/default.aspx/article.asp?issn=2071-3592;year=2023;volume=17;issue=1;spage=18;epage=22;aulast=Wang
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author Xian-He Shyanher Wang
author_facet Xian-He Shyanher Wang
author_sort Xian-He Shyanher Wang
collection DOAJ
description Background: Nitric oxide (NO) is a colorless and odorless toxic gas and a short-acting physiological vasodilator. NO is produced by nitric oxide synthase (NOS). NOS has three isoforms, including endothelium NOS, neuronal NOS, and inducible NOS (iNOS). Many NOS inhibitors are analogs for the amino acid, L-arginine, and are nonselective among the three NOS isoforms. Alternatively, mercaptoethylguanidine (MEG) is not an analog for the amino acid but an analog for the guanidine group on L-arginine. Concentrations of up to 10-4 M have no effects on the acetylcholine-induced endothelium-dependent relaxations in rat aorta, but it reverses sepsis-induced vascular hypocontractility in endothelium-removed rat aorta. Objectives: The pulmonary artery is different from the aorta in many physiological responses. This study aims to investigate the selectivity of MEG for the iNOS in the pulmonary artery. Methods: Standardized rabbit pulmonary arterial rings were adopted. MEG of up to 10-4 M was added to the tissue baths containing either the endothelium-intact or -removed rings after testing for endothelial function. Phenylephrine concentration-response curves were cumulatively obtained after the incubation period, p and compared among four groups, including control, MEG alone, IL-1β alone, and IL-1β plus MEG. Results: Acetylcholine could stimulate the endothelium NOS on the endothelium-intact pulmonary arterial rings under the tonic status, resulting inrelaxation, but not on the endothelium-removed ones. Interleukin (IL)-1β could stimulate the iNOS in both the endothelium-intact and endothelium-removed pulmonary arterial rings after tissue incubation, resulting in relaxation. The IL-1β-induced relaxation could be inhibited by mercaptoethylguanidine (MEG) in both the endothelium-intact and endothelium-removed pulmonary arterial rings. MEG had no effects on both the endothelium-intact or endothelium-removed pulmonary arterial rings. Conclusion: MEG is a selective iNOS inhibitor in the pulmonary artery.
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spelling doaj.art-82ede9d3605540e59508a957322f49ab2024-02-20T15:46:54ZengWolters Kluwer Medknow PublicationsTungs’ Medical Journal2071-35922023-01-01171182210.4103/ETMJ.TMJ-110017Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary arteryXian-He Shyanher WangBackground: Nitric oxide (NO) is a colorless and odorless toxic gas and a short-acting physiological vasodilator. NO is produced by nitric oxide synthase (NOS). NOS has three isoforms, including endothelium NOS, neuronal NOS, and inducible NOS (iNOS). Many NOS inhibitors are analogs for the amino acid, L-arginine, and are nonselective among the three NOS isoforms. Alternatively, mercaptoethylguanidine (MEG) is not an analog for the amino acid but an analog for the guanidine group on L-arginine. Concentrations of up to 10-4 M have no effects on the acetylcholine-induced endothelium-dependent relaxations in rat aorta, but it reverses sepsis-induced vascular hypocontractility in endothelium-removed rat aorta. Objectives: The pulmonary artery is different from the aorta in many physiological responses. This study aims to investigate the selectivity of MEG for the iNOS in the pulmonary artery. Methods: Standardized rabbit pulmonary arterial rings were adopted. MEG of up to 10-4 M was added to the tissue baths containing either the endothelium-intact or -removed rings after testing for endothelial function. Phenylephrine concentration-response curves were cumulatively obtained after the incubation period, p and compared among four groups, including control, MEG alone, IL-1β alone, and IL-1β plus MEG. Results: Acetylcholine could stimulate the endothelium NOS on the endothelium-intact pulmonary arterial rings under the tonic status, resulting inrelaxation, but not on the endothelium-removed ones. Interleukin (IL)-1β could stimulate the iNOS in both the endothelium-intact and endothelium-removed pulmonary arterial rings after tissue incubation, resulting in relaxation. The IL-1β-induced relaxation could be inhibited by mercaptoethylguanidine (MEG) in both the endothelium-intact and endothelium-removed pulmonary arterial rings. MEG had no effects on both the endothelium-intact or endothelium-removed pulmonary arterial rings. Conclusion: MEG is a selective iNOS inhibitor in the pulmonary artery.https://journals.lww.com/TMJ/Pages/default.aspx/article.asp?issn=2071-3592;year=2023;volume=17;issue=1;spage=18;epage=22;aulast=Wanginterleukin-1βmercaptoethylguanidinenitric oxidenitric oxide synthasepulmonary artery
spellingShingle Xian-He Shyanher Wang
Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
Tungs’ Medical Journal
interleukin-1β
mercaptoethylguanidine
nitric oxide
nitric oxide synthase
pulmonary artery
title Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
title_full Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
title_fullStr Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
title_full_unstemmed Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
title_short Mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
title_sort mercaptoethylguanidine is a selective inducible nitric oxide synthase inhibitor on pulmonary artery
topic interleukin-1β
mercaptoethylguanidine
nitric oxide
nitric oxide synthase
pulmonary artery
url https://journals.lww.com/TMJ/Pages/default.aspx/article.asp?issn=2071-3592;year=2023;volume=17;issue=1;spage=18;epage=22;aulast=Wang
work_keys_str_mv AT xianheshyanherwang mercaptoethylguanidineisaselectiveinduciblenitricoxidesynthaseinhibitoronpulmonaryartery