Impact of kinins in the treatment of cardiovascular diseases

Regoli, Doménico; Plante, Gérard E.; Gobeil, Fernand

doi:10.1016/j.pharmthera.2012.04.002

Cited by 71 publications

(80 citation statements)

References 259 publications

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“…b. Bradykinin receptors. The contributions of bradykinin (BK) receptors (B 1 R and B 2 R) to pain, inflammation, and TRP channel activation has been the subject of multiple reviews (Peth} o and Reeh, 2012;Regoli et al, 2012;Blaes and Girolami, 2013). Proteases of the kallikrein-kininogen system cleave propeptides to produce painful ligands of the kinin family.…”

Section: G Protein-coupled Receptors That Sense Noxious Stimuli Anmentioning

confidence: 99%

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Veldhuis¹,

Poole²,

Grace³

et al. 2014

Pharmacol Rev

139

135

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Section: G Protein-coupled Receptors That Sense Noxious Stimuli Anmentioning

confidence: 99%

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Veldhuis¹,

Poole²,

Grace³

et al. 2014

Pharmacol Rev

139

135

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“…Because aliskiren increases bradykinin levels in the heart 12 and bradykinin has well-established cardioprotective activity, [13][14][15][16][17][18][19][20][21][22] we compared the effects of aliskiren with valsartan and their combination on cardiac I/R injury. Myocardial infarct size relative to the area at risk was 43% in the no inhibitor vehicle-treated group (Figure 1).…”

Section: Aliskiren Reduces Cardiac I/r Injurymentioning

confidence: 99%

“…12 Both the dose-response and time course of the aliskiren-induced increases in cardiac bradykinin levels suggested that these actions of aliskiren were independent of renin inhibition. 12 Bradykinin has well-established cardioprotective activity [13][14][15][16][17][18][19][20][21][22] and is implicated in the reduction of myocardial ischemiareperfusion (I/R) injury by both ACE inhibitors and ARBs. The bradykinin receptor type 2 (B 2 ) receptor antagonist icatibant prevents the reduction in I/R injury produced by ACE inhibitors, [23][24][25][26] whereas both icatibant and the angiotensin II receptor type 2 (AT 2 ) receptor antagonist PD123319 attenuate cardioprotection by ARBs.…”

mentioning

confidence: 99%

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

2014

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Abstract-Angiotensin-converting enzyme inhibitors and angiotensin AT 1 receptor blockers reduce myocardial ischemiareperfusion injury via bradykinin B 2 receptor-and angiotensin AT 2 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 B 2 and AT 2 receptors in this effect. Female SpragueDawley rats were treated with aliskiren (10 mg/kg per day) and valsartan (30 mg/kg per day), alone or in combination, together with the B 2 receptor antagonist icatibant (0.5 mg/kg per day) or the AT 2 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 B 2 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 B 2 receptor-and AT 2 receptor-mediated mechanism, whereas cardioprotection by valsartan is mediated via the AT 2 receptor. In addition, aliskiren attenuates valsartan-induced increases in angiotensin II levels, thus preventing AT 2 receptor-mediated cardioprotection by valsartan. MethodsDetailed methods are provided in the online-only Data Supplement. Results Effects of Drug Treatment on Systolic BloodPressure, Body Weight, Heart Weight/Body Weight Ratio, and Mean Arterial Blood Pressure During I/R Injury Systolic blood pressure (SBP) of the 12 groups of rats during the 4-week treatment period before I/R injury is shown in the Table. In the present study, we used doses of aliskiren (10 mg/kg per day SC) and valsartan (30 mg/kg per day PO) that have little effect on blood pressure in normotensive Sprague-Dawley rats. Neither aliskiren nor valsartan caused any change in SBP during the 4 weeks (Table). However, SBP in rats receiving the combination of aliskiren plus valsartan was less than that in vehicle-treated rats. In contrast, SBP in rats receiving the B 2 receptor antagonist icatibant (0.5 mg/kg per day SC) alone was higher than that of vehicle-treated rats. Rats treated with aliskiren, valsartan, and the combination of aliskiren plus valsartan had lower SBP during combined treatment with icatibant than that of rats treated with icatibant alone. Treatment with the AT 2 receptor antagonist PD123319 (30 mg/kg per day SC) alone did not affect blood pressure. During combined treatment w...

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“…A potential treatment target is the angiotensin system, a major determinant of carotid plaque instability and stroke risk. 13 Angiotensin II stimulates adventitial neovascularity and is implicated in animal models of IPH.…”

Section: Abbreviationsmentioning

confidence: 99%

Vitamin D and Vulnerable Carotid Plaque

McNally

Burton²,

Aldred

et al. 2016

AJNR Am J Neuroradiol

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Impact of kinins in the treatment of cardiovascular diseases

Cited by 71 publications

References 259 publications

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism

Vitamin D and Vulnerable Carotid Plaque

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Impact of kinins in the treatment of cardiovascular diseases

Cited by 71 publications

References 259 publications

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B 2 Receptor– and Angiotensin AT 2 Receptor–Mediated Mechanism

Vitamin D and Vulnerable Carotid Plaque

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Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B ₂ Receptor– and Angiotensin AT ₂ Receptor–Mediated Mechanism