Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension
The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, i...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1151308/full |
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| author | Zuzana Husková Soňa Kikerlová Matúš Miklovič Matúš Miklovič Petr Kala Petr Kala František Papoušek Jan Neckář Jan Neckář |
| author_facet | Zuzana Husková Soňa Kikerlová Matúš Miklovič Matúš Miklovič Petr Kala Petr Kala František Papoušek Jan Neckář Jan Neckář |
| author_sort | Zuzana Husková |
| collection | DOAJ |
| description | The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male Cyp1a1-Ren-2 transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins’ levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase. |
| first_indexed | 2024-03-13T05:38:00Z |
| format | Article |
| id | doaj.art-dbb7ae5a5b584842a647aa93460a5c97 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-13T05:38:00Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-dbb7ae5a5b584842a647aa93460a5c972023-06-14T05:23:33ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-06-011410.3389/fphys.2023.11513081151308Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertensionZuzana Husková0Soňa Kikerlová1Matúš Miklovič2Matúš Miklovič3Petr Kala4Petr Kala5František Papoušek6Jan Neckář7Jan Neckář8Center of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, CzechiaCenter of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, CzechiaCenter of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, CzechiaDepartment of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, CzechiaCenter of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, CzechiaDepartment of Cardiology, 2nd Medical Faculty, Charles University and University Hospital Motol, Prague, CzechiaLaboratory of Developmental Cardiology, Institute of Physiology, Academy of Sciences of the Czech Republic (ASCR), Prague, CzechiaCenter of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, CzechiaLaboratory of Developmental Cardiology, Institute of Physiology, Academy of Sciences of the Czech Republic (ASCR), Prague, CzechiaThe aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male Cyp1a1-Ren-2 transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins’ levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase.https://www.frontiersin.org/articles/10.3389/fphys.2023.1151308/fullrenin-angiotensin systemischemia/reperfusion injuryANG II-dependent hypertensionAT1 receptor antagonistP-V analysis |
| spellingShingle | Zuzana Husková Soňa Kikerlová Matúš Miklovič Matúš Miklovič Petr Kala Petr Kala František Papoušek Jan Neckář Jan Neckář Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension Frontiers in Physiology renin-angiotensin system ischemia/reperfusion injury ANG II-dependent hypertension AT1 receptor antagonist P-V analysis |
| title | Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension |
| title_full | Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension |
| title_fullStr | Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension |
| title_full_unstemmed | Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension |
| title_short | Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension |
| title_sort | inappropriate activation of the renin angiotensin system improves cardiac tolerance to ischemia reperfusion injury in rats with late angiotensin ii dependent hypertension |
| topic | renin-angiotensin system ischemia/reperfusion injury ANG II-dependent hypertension AT1 receptor antagonist P-V analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1151308/full |
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