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Aliskiren reduces myocardial ischemia-reperfusion injury by a bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanism.
Hypertension. 2014 Apr; 63(4):768-73.H

Abstract

Angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor blockers reduce myocardial ischemia-reperfusion injury via bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanisms. The renin inhibitor aliskiren increases cardiac tissue kallikrein and bradykinin levels. In the present study, we investigated the effect of aliskiren on myocardial ischemia-reperfusion injury and the roles of B2 and AT2 receptors in this effect. Female Sprague-Dawley rats were treated with aliskiren (10 mg/kg per day) and valsartan (30 mg/kg per day), alone or in combination, together with the B2 receptor antagonist icatibant (0.5 mg/kg per day) or the AT2 receptor antagonist PD123319 (30 mg/kg per day), for 4 weeks before myocardial ischemia-reperfusion injury. Aliskiren increased cardiac bradykinin levels and attenuated valsartan-induced increases in plasma angiotensin II levels. In vehicle-treated rats, myocardial infarct size (% area at risk, mean±SEM, n=7-13) was 43±3%. This was reduced to a similar extent by aliskiren, valsartan, and their combination to 24±3%, 25±3%, and 22±2%, respectively. Icatibant reversed the cardioprotective effects of aliskiren and the combination of aliskiren plus valsartan, but not valsartan alone, indicating that valsartan-induced cardioprotection was not mediated by the B2 receptor. PD123319 reversed the cardioprotective effects of aliskiren, valsartan, and the combination of aliskiren plus valsartan. Aliskiren protects the heart from myocardial ischemia-reperfusion injury via a B2 receptor- and AT2 receptor-mediated mechanism, whereas cardioprotection by valsartan is mediated via the AT2 receptor. In addition, aliskiren attenuates valsartan-induced increases in angiotensin II levels, thus preventing AT2 receptor-mediated cardioprotection by valsartan.

Authors+Show Affiliations

St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. dcampbell@svi.edu.au.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24420538

Citation

Koid, Suang Suang, et al. "Aliskiren Reduces Myocardial Ischemia-reperfusion Injury By a Bradykinin B2 Receptor- and Angiotensin AT2 Receptor-mediated Mechanism." Hypertension (Dallas, Tex. : 1979), vol. 63, no. 4, 2014, pp. 768-73.
Koid SS, Ziogas J, Campbell DJ. Aliskiren reduces myocardial ischemia-reperfusion injury by a bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanism. Hypertension. 2014;63(4):768-73.
Koid, S. S., Ziogas, J., & Campbell, D. J. (2014). Aliskiren reduces myocardial ischemia-reperfusion injury by a bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanism. Hypertension (Dallas, Tex. : 1979), 63(4), 768-73. https://doi.org/10.1161/HYPERTENSIONAHA.113.02902
Koid SS, Ziogas J, Campbell DJ. Aliskiren Reduces Myocardial Ischemia-reperfusion Injury By a Bradykinin B2 Receptor- and Angiotensin AT2 Receptor-mediated Mechanism. Hypertension. 2014;63(4):768-73. PubMed PMID: 24420538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aliskiren reduces myocardial ischemia-reperfusion injury by a bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanism. AU - Koid,Suang Suang, AU - Ziogas,James, AU - Campbell,Duncan John, Y1 - 2014/01/13/ PY - 2014/1/15/entrez PY - 2014/1/15/pubmed PY - 2014/6/3/medline KW - aliskiren KW - angiotensins KW - bradykinin KW - myocardial infarction SP - 768 EP - 73 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 63 IS - 4 N2 - Angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor blockers reduce myocardial ischemia-reperfusion injury via bradykinin B2 receptor- and angiotensin AT2 receptor-mediated mechanisms. The renin inhibitor aliskiren increases cardiac tissue kallikrein and bradykinin levels. In the present study, we investigated the effect of aliskiren on myocardial ischemia-reperfusion injury and the roles of B2 and AT2 receptors in this effect. Female Sprague-Dawley rats were treated with aliskiren (10 mg/kg per day) and valsartan (30 mg/kg per day), alone or in combination, together with the B2 receptor antagonist icatibant (0.5 mg/kg per day) or the AT2 receptor antagonist PD123319 (30 mg/kg per day), for 4 weeks before myocardial ischemia-reperfusion injury. Aliskiren increased cardiac bradykinin levels and attenuated valsartan-induced increases in plasma angiotensin II levels. In vehicle-treated rats, myocardial infarct size (% area at risk, mean±SEM, n=7-13) was 43±3%. This was reduced to a similar extent by aliskiren, valsartan, and their combination to 24±3%, 25±3%, and 22±2%, respectively. Icatibant reversed the cardioprotective effects of aliskiren and the combination of aliskiren plus valsartan, but not valsartan alone, indicating that valsartan-induced cardioprotection was not mediated by the B2 receptor. PD123319 reversed the cardioprotective effects of aliskiren, valsartan, and the combination of aliskiren plus valsartan. Aliskiren protects the heart from myocardial ischemia-reperfusion injury via a B2 receptor- and AT2 receptor-mediated mechanism, whereas cardioprotection by valsartan is mediated via the AT2 receptor. In addition, aliskiren attenuates valsartan-induced increases in angiotensin II levels, thus preventing AT2 receptor-mediated cardioprotection by valsartan. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/24420538/Aliskiren_reduces_myocardial_ischemia_reperfusion_injury_by_a_bradykinin_B2_receptor__and_angiotensin_AT2_receptor_mediated_mechanism_ L2 - https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.113.02902?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -