Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation
Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor—G<sub>q/11</sub> signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modul...
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/724 |
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| author | Zsuzsanna Miklós Dina Wafa György L. Nádasy Zsuzsanna E. Tóth Balázs Besztercei Gabriella Dörnyei Zsófia Laska Zoltán Benyó Tamás Ivanics László Hunyady Mária Szekeres |
| author_facet | Zsuzsanna Miklós Dina Wafa György L. Nádasy Zsuzsanna E. Tóth Balázs Besztercei Gabriella Dörnyei Zsófia Laska Zoltán Benyó Tamás Ivanics László Hunyady Mária Szekeres |
| author_sort | Zsuzsanna Miklós |
| collection | DOAJ |
| description | Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor—G<sub>q/11</sub> signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB<sub>1</sub>R) in these effects. Expression of CB<sub>1</sub>R in rat cardiac tissue was confirmed by immunohistochemistry. To characterize short-term Ang II effects, increasing concentrations of Ang II (10<sup>−9</sup>–10<sup>−7</sup> M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10<sup>−7</sup> M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB<sub>1</sub>R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB<sub>1</sub>R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB<sub>1</sub>R may counteract the positive inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction. |
| first_indexed | 2024-03-10T12:57:37Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:57:37Z |
| publishDate | 2021-03-01 |
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| spelling | doaj.art-eeaf57e72eec4c48bdaaa7fbdfa63c3e2023-11-21T11:51:14ZengMDPI AGCells2073-44092021-03-0110472410.3390/cells10040724Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor ActivationZsuzsanna Miklós0Dina Wafa1György L. Nádasy2Zsuzsanna E. Tóth3Balázs Besztercei4Gabriella Dörnyei5Zsófia Laska6Zoltán Benyó7Tamás Ivanics8László Hunyady9Mária Szekeres10Institute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Anatomy, Histology and Embryology, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Morphology and Physiology, Semmelweis University, 1088 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, 1094 Budapest, HungaryAngiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor—G<sub>q/11</sub> signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB<sub>1</sub>R) in these effects. Expression of CB<sub>1</sub>R in rat cardiac tissue was confirmed by immunohistochemistry. To characterize short-term Ang II effects, increasing concentrations of Ang II (10<sup>−9</sup>–10<sup>−7</sup> M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10<sup>−7</sup> M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB<sub>1</sub>R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB<sub>1</sub>R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB<sub>1</sub>R may counteract the positive inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction.https://www.mdpi.com/2073-4409/10/4/724Angiotensin IIcardiacendocannabinoidCB<sub>1</sub> cannabinoid receptormyocardial functioncoronary flow |
| spellingShingle | Zsuzsanna Miklós Dina Wafa György L. Nádasy Zsuzsanna E. Tóth Balázs Besztercei Gabriella Dörnyei Zsófia Laska Zoltán Benyó Tamás Ivanics László Hunyady Mária Szekeres Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation Cells Angiotensin II cardiac endocannabinoid CB<sub>1</sub> cannabinoid receptor myocardial function coronary flow |
| title | Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation |
| title_full | Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation |
| title_fullStr | Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation |
| title_full_unstemmed | Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation |
| title_short | Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB<sub>1</sub> Receptor Activation |
| title_sort | angiotensin ii induced cardiac effects are modulated by endocannabinoid mediated cb sub 1 sub receptor activation |
| topic | Angiotensin II cardiac endocannabinoid CB<sub>1</sub> cannabinoid receptor myocardial function coronary flow |
| url | https://www.mdpi.com/2073-4409/10/4/724 |
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