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Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries
Picotamide is a thromboxane A(2) (TXA(2)) receptor antagonist and TXA(2) synthase inhibitor. In clinical studies, it has been considered as a platelet aggregation inhibitor and improved renal function. In vitro studies suggested inhibition of smooth muscle contraction by picotamide, which is poorly...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085950/ https://www.ncbi.nlm.nih.gov/pubmed/33929093 http://dx.doi.org/10.1002/prp2.771 |
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author | Li, Bingsheng Huang, Ru Wang, Ruixiao Liu, Yuhan Stief, Christian G. Hennenberg, Martin |
author_facet | Li, Bingsheng Huang, Ru Wang, Ruixiao Liu, Yuhan Stief, Christian G. Hennenberg, Martin |
author_sort | Li, Bingsheng |
collection | PubMed |
description | Picotamide is a thromboxane A(2) (TXA(2)) receptor antagonist and TXA(2) synthase inhibitor. In clinical studies, it has been considered as a platelet aggregation inhibitor and improved renal function. In vitro studies suggested inhibition of smooth muscle contraction by picotamide, which is poorly understood. Here, we examined effects of picotamide on contractions of renal interlobar and coronary porcine arteries, induced by different vasoconstrictors. Contractions were induced in an organ bath by agonists or electric field stimulation (EFS). Picotamide inhibited EFS‐induced contractions of interlobar arteries around 50% using concentrations of 100 and 300 µM. In interlobar arteries, concentration response curves for contractions induced by three different α(1)‐adrenoceptor agonists were shifted to the right by picotamide (2–10‐fold increases in EC(50)). In coronary arteries, α(1)‐adrenergic contractions were inhibited without right shift (approx. 50%). Contractions induced by two different cholinergic agonists in coronary arteries were inhibited by picotamide (≥50%) withouth right shift. Inhibition of serotonin‐induced contractions by picotamide showed features of a right shift, whereas contractions induced by the TXA(2) analog U46619, angiotensin‐II, and endothelin‐1 were inhibited by picotamide in interlobar and coronary arteries without right shifts and to different degree. Picotamide inhibits a wide spectrum of vasoconstrictor‐induced contractions in porcine interlobar and coronary arteries. Inhibition of vasocontraction may contribute to beneficial effects of picotamide in the cardiovascular system and kidney. |
format | Online Article Text |
id | pubmed-8085950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80859502021-05-07 Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries Li, Bingsheng Huang, Ru Wang, Ruixiao Liu, Yuhan Stief, Christian G. Hennenberg, Martin Pharmacol Res Perspect Original Articles Picotamide is a thromboxane A(2) (TXA(2)) receptor antagonist and TXA(2) synthase inhibitor. In clinical studies, it has been considered as a platelet aggregation inhibitor and improved renal function. In vitro studies suggested inhibition of smooth muscle contraction by picotamide, which is poorly understood. Here, we examined effects of picotamide on contractions of renal interlobar and coronary porcine arteries, induced by different vasoconstrictors. Contractions were induced in an organ bath by agonists or electric field stimulation (EFS). Picotamide inhibited EFS‐induced contractions of interlobar arteries around 50% using concentrations of 100 and 300 µM. In interlobar arteries, concentration response curves for contractions induced by three different α(1)‐adrenoceptor agonists were shifted to the right by picotamide (2–10‐fold increases in EC(50)). In coronary arteries, α(1)‐adrenergic contractions were inhibited without right shift (approx. 50%). Contractions induced by two different cholinergic agonists in coronary arteries were inhibited by picotamide (≥50%) withouth right shift. Inhibition of serotonin‐induced contractions by picotamide showed features of a right shift, whereas contractions induced by the TXA(2) analog U46619, angiotensin‐II, and endothelin‐1 were inhibited by picotamide in interlobar and coronary arteries without right shifts and to different degree. Picotamide inhibits a wide spectrum of vasoconstrictor‐induced contractions in porcine interlobar and coronary arteries. Inhibition of vasocontraction may contribute to beneficial effects of picotamide in the cardiovascular system and kidney. John Wiley and Sons Inc. 2021-04-30 /pmc/articles/PMC8085950/ /pubmed/33929093 http://dx.doi.org/10.1002/prp2.771 Text en © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Li, Bingsheng Huang, Ru Wang, Ruixiao Liu, Yuhan Stief, Christian G. Hennenberg, Martin Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title | Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title_full | Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title_fullStr | Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title_full_unstemmed | Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title_short | Picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
title_sort | picotamide inhibits a wide spectrum of agonist‐induced smooth muscle contractions in porcine renal interlobar and coronary arteries |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085950/ https://www.ncbi.nlm.nih.gov/pubmed/33929093 http://dx.doi.org/10.1002/prp2.771 |
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