Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs
Soluble guanylate cyclase (sGC) stimulator riociguat is a relatively novel therapeutic agent for pulmonary hypertension (PH) in human medicine. Riociguat induces endothelium-independent pulmonary artery (PA) relaxation by directly activating the sGC-cyclic guanosine-3′,5′-monophosphate (cGMP) pathwa...
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MDPI AG
2023-02-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/10/2/159 |
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| author | Satoshi Kameshima Yuki Nakamura Kenji Uehara Tomoko Kodama Hideyuki Yamawaki Kotaro Nishi Shozo Okano Ryo Niijima Yuya Kimura Naoyuki Itoh |
| author_facet | Satoshi Kameshima Yuki Nakamura Kenji Uehara Tomoko Kodama Hideyuki Yamawaki Kotaro Nishi Shozo Okano Ryo Niijima Yuya Kimura Naoyuki Itoh |
| author_sort | Satoshi Kameshima |
| collection | DOAJ |
| description | Soluble guanylate cyclase (sGC) stimulator riociguat is a relatively novel therapeutic agent for pulmonary hypertension (PH) in human medicine. Riociguat induces endothelium-independent pulmonary artery (PA) relaxation by directly activating the sGC-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway in muscle cells. Although riociguat may be effective in the treatment of dogs with refractory PH, basic studies on its clinical application in veterinary medicine are lacking. The present study aimed to explore the effects of riociguat on the contractility of an isolated canine PA and the hemodynamics of dogs with acute PH. In an isolated endothelium-denuded canine PA, the effects of riociguat on endothelin (ET)-1-induced contraction and cGMP levels were investigated using the Magnus method and ELISA, respectively. The effect of riociguat on the hemodynamics of the thromboxane A2 analog U46619-induced PH model dog was examined by invasive catheterization. Riociguat increased cGMP levels and reduced ET-1-induced contraction of the isolated PA. Riociguat inhibited the U46619-induced elevation of PA pressure and pulmonary vascular resistance and increased cardiac output, but it had no effect on basal systemic blood pressure. These results demonstrate for the first time that riociguat can inhibit the elevation of PA pressure through PA relaxation via an endothelium-independent increase in cGMP in dogs with PH. |
| first_indexed | 2024-03-11T08:02:02Z |
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| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-11T08:02:02Z |
| publishDate | 2023-02-01 |
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| series | Veterinary Sciences |
| spelling | doaj.art-a079923670774de2a6db7cd41f1eed392023-11-16T23:46:26ZengMDPI AGVeterinary Sciences2306-73812023-02-0110215910.3390/vetsci10020159Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in DogsSatoshi Kameshima0Yuki Nakamura1Kenji Uehara2Tomoko Kodama3Hideyuki Yamawaki4Kotaro Nishi5Shozo Okano6Ryo Niijima7Yuya Kimura8Naoyuki Itoh9Laboratory of Small Animal Internal Medicine 1, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Internal Medicine 1, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Internal Medicine 1, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanSmall Animal Teaching Hospital, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Internal Medicine 1, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanLaboratory of Small Animal Internal Medicine 1, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada 034-8628, Aomori, JapanSoluble guanylate cyclase (sGC) stimulator riociguat is a relatively novel therapeutic agent for pulmonary hypertension (PH) in human medicine. Riociguat induces endothelium-independent pulmonary artery (PA) relaxation by directly activating the sGC-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway in muscle cells. Although riociguat may be effective in the treatment of dogs with refractory PH, basic studies on its clinical application in veterinary medicine are lacking. The present study aimed to explore the effects of riociguat on the contractility of an isolated canine PA and the hemodynamics of dogs with acute PH. In an isolated endothelium-denuded canine PA, the effects of riociguat on endothelin (ET)-1-induced contraction and cGMP levels were investigated using the Magnus method and ELISA, respectively. The effect of riociguat on the hemodynamics of the thromboxane A2 analog U46619-induced PH model dog was examined by invasive catheterization. Riociguat increased cGMP levels and reduced ET-1-induced contraction of the isolated PA. Riociguat inhibited the U46619-induced elevation of PA pressure and pulmonary vascular resistance and increased cardiac output, but it had no effect on basal systemic blood pressure. These results demonstrate for the first time that riociguat can inhibit the elevation of PA pressure through PA relaxation via an endothelium-independent increase in cGMP in dogs with PH.https://www.mdpi.com/2306-7381/10/2/159cardiac outputcyclic guanosine monophosphatedogendothelial dysfunctionpulmonary arterial contractilitypulmonary hypertension |
| spellingShingle | Satoshi Kameshima Yuki Nakamura Kenji Uehara Tomoko Kodama Hideyuki Yamawaki Kotaro Nishi Shozo Okano Ryo Niijima Yuya Kimura Naoyuki Itoh Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs Veterinary Sciences cardiac output cyclic guanosine monophosphate dog endothelial dysfunction pulmonary arterial contractility pulmonary hypertension |
| title | Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs |
| title_full | Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs |
| title_fullStr | Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs |
| title_full_unstemmed | Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs |
| title_short | Effects of a Soluble Guanylate Cyclase Stimulator Riociguat on Contractility of Isolated Pulmonary Artery and Hemodynamics of U46619-Induced Pulmonary Hypertension in Dogs |
| title_sort | effects of a soluble guanylate cyclase stimulator riociguat on contractility of isolated pulmonary artery and hemodynamics of u46619 induced pulmonary hypertension in dogs |
| topic | cardiac output cyclic guanosine monophosphate dog endothelial dysfunction pulmonary arterial contractility pulmonary hypertension |
| url | https://www.mdpi.com/2306-7381/10/2/159 |
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