Acute Antihypertrophic Actions of Bradykinin in the Rat Heart

Rosenkranz, A; Hood, Sally G.; Woods, Robyn L.; Dusting, Gregory J.; Ritchie, Rebecca H

doi:10.1161/01.hyp.0000032854.74042.cf

Cited by 35 publications

(34 citation statements)

References 49 publications

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“…17,18 Recent evidence indicates that increased cyclic GMP is essential for the antihypertrophic action of bradykinin in isolated rat hearts exposed to Ang II. 19 Conversely, deletion of B2R gene makes 2-renin gene 129/J uniquely prone to the development of decompensated cardiomyopathy with aging. 3 Even more precocious is the occurrence of ventricular dysfunction in 129/J lacking the TK gene.…”

Section: Cardiac Parameters In Wild-type and B2r Knockout Micementioning

confidence: 99%

Cardiac Hypertrophy and Microvascular Deficit in Kinin B2 Receptor Knockout Mice

et al. 2003

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Abstract-Experimental and clinical evidence suggests kinin involvement in adaptive myocardial growth. Kinins are growth-inhibitory to cardiomyocytes. Knockout of kinin B2 receptor (B2R) signaling causes dilated and failing cardiomyopathy in 129/J mice, and a 9-bp deletion polymorphism of human B2R is associated with reduced receptor expression and exaggerated left ventricular growth response to physical stress. We reasoned that genetic background and aging may significantly influence the impact of B2R mutation on cardiac phenotype. The theory was challenged in C57BL/6 mice, a strain that naturally differs from the 129/J strain, carrying 1 instead of 2 renin genes. C57BL/6 B2R knockouts (B2R-KO) showed higher blood pressure and heart rate levels (PϽ0.05) compared with wild-type controls (WT) at all ages examined. At 12 months, left ventricular contractility and diastolic function were mildly altered (PϽ0.05) and histological and morphological analyses revealed ventricular hypertrophy and cardiomyocyte enlargement in B2R-KO (PϽ0.01). Reparative fibrosis was enhanced by 208% and capillary density reduced by 38% (PϽ0.01).Functional and structural alterations induced by B2R deletion in C57BL/6 mice were less severe than those reported previously in the 129/J strain. We conclude that interaction of B2R signaling with other genetic determinants influences aging-related changes in myocardial structure and function. These findings may help us understand the role of kinins in the development of cardiac failure.

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Section: Cardiac Parameters In Wild-type and B2r Knockout Micementioning

confidence: 99%

Cardiac Hypertrophy and Microvascular Deficit in Kinin B2 Receptor Knockout Mice

et al. 2003

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“…Several recent reports suggest that activation of the B2-kinin receptors (B2R) could reduce the proliferative effect of several growth factors in cultured cell lines (15,45,50) and in mesangial cells (1,18). B2-kinin receptor is involved in the antihypertrophic effect of BK documented in cultured cardiomyocytes (30,52,53,55) but also in vivo, mainly in the heart (24,25,40,56). Moreover, the antihypertrophic effect of BK in vivo on the renal vasculature in mice has been also reported (67).…”

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ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats

Allard¹,

Buléon²,

Cellier³

et al. 2007

American Journal of Physiology-Renal Physiology

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Tack I, Girolami J-P. ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats. Am J Physiol Renal Physiol 293: F1083-F1092, 2007. First published June 27, 2007; doi:10.1152/ajprenal.00401.2006 is associated with increased oxidative stress, overexpression and activation of growth factor receptors, including those for transforming growth factor-␤1 (TGF-␤-RII), platelet-derived growth factor (PDGF-R), and insulin-like growth factor (IGF1-R). These pathways are believed to represent pathophysiological determinants of DN. Beyond perfect glycemic control, angiotensin-converting enzyme inhibitors (ACEI) are the most efficient treatment to delay glomerulosclerosis. Since their mechanisms of action remain uncertain, we investigated the effect of ACEI on the glomerular expression of these growth factor pathways in a model of streptozotocin-induced diabetes in rats. The early phase of diabetes was found to be associated with an increase in glomerular expression of IGF1-R, PDGF-R, and TGF-␤-RII and activation of IRS1, Erk 1/2, and Smad 2/3. These changes were significantly reduced by ACEI treatment. Furthermore, ACEI stimulated glutathione peroxidase activity, suggesting a protective role against oxidative stress. ACEI decreased ANG II production but also increased bradykinin bioavailability by reducing its degradation. Thus the involvement of the bradykinin pathway was investigated using coadministration of HOE-140, a highly specific nonpeptidic B2-kinin receptor antagonist. Almost all the previously described effects of ACEI were abolished by HOE-140, as was the increase in glutathione peroxidase activity. Moreover, the well-established ability of ACEI to reduce albuminuria was also prevented by HOE-140. Taken together, these data demonstrate that, in the early phase of diabetes, ACEI reverse glomerular overexpression and activation of some critical growth factor pathways and increase protection against oxidative stress and that these effects involve B2-kinin receptor activation.angiotensin-converting enzyme inhibitor; oxidative stress; glutathione peroxidase activity; diabetes DIABETIC NEPHROPATHY (DN) causes the majority of end-stage renal diseases throughout the world (54). It was initially believed that elevated blood glucose was the major cause of renal damage in both type 1 and 2 diabetes. However, several clinical studies have demonstrated that strict glycemic control is not sufficient to prevent the progression of renal dysfunction and the development of glomerular lesions. The mechanisms underlying the progression of diabetic kidney disease are intricate and still not completely understood. Among the many pathophysiological mechanisms possible, several growth factors and cytokines have been put forward to account for the onset of DN. This is particularly the case for the paracrine expression of insulin-like growth factor-1 (IGF-1), transforming growth factor-␤ (TGF-␤) (20), and platelet-derived growth factor (PDG...

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confidence: 99%

“…We previously demonstrated that bradykinin prevents acute myocardial hypertrophy in vitro by stimulating the release of endothelial nitric oxide (NO) (3) to elevate cardiomyocyte guanosine 3Ј,5Ј-cyclic monophosphate (cyclic GMP) (4). This pathway also contributes to the antihypertrophic actions of ACE inhibitors (4,5). Endothelial NO dysfunction induced by high glucose abolishes the antihypertrophic and cyclic GMP-stimulatory effects of bradykinin in isolated cardiomyocytes (6), and there is evidence that antihypertrophic ACE inhibitor efficacy is compromised in experimental diabetes (7)(8)(9) and diabetic patients (10).…”

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confidence: 99%

B-Type Natriuretic Peptide Prevents Acute Hypertrophic Responses in the Diabetic Rat Heart

et al. 2003

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Stimulation of cardiomyocyte guanosine 3,5-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In cardiomyocyte/endothelial cell cocultures, bradykinin efficacy is abolished by highglucose-induced endothelial NO dysfunction. We now demonstrate that antihypertrophic actions of natriuretic peptides, which stimulate cyclic GMP independently of NO, are preserved in cardiomyocytes despite high-glucose-induced endothelial dysfunction. Further, streptozotocin-induced diabetes significantly impairs the effectiveness of acute antihypertrophic strategies in isolated rat hearts. In hearts from citrate-treated control rats, angiotensin II-stimulated [ 3 H]phenylalanine incorporation and atrial natriuretic peptide and ␤-myosin heavy chain mRNA expression were prevented by B-type natriuretic peptide (BNP), bradykinin, the ACE inhibitor ramiprilat, and the neutral endopeptidase inhibitor candoxatrilat. These antihypertrophic effects were accompanied by increased left ventricular cyclic GMP. In age-matched diabetic hearts, the antihypertrophic and cyclic GMP stimulatory actions of bradykinin, ramiprilat, and candoxatrilat were absent. However, the blunting of hypertrophic markers and accompanying increases in cyclic GMP stimulated by BNP were preserved in diabetes. Thus BNP, which increases cyclic GMP independently of NO, is an important approach to prevent growth in the diabetic myocardium, where endothelium-dependent mechanisms are compromised.

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Acute Antihypertrophic Actions of Bradykinin in the Rat Heart

Cited by 35 publications

References 49 publications

Cardiac Hypertrophy and Microvascular Deficit in Kinin B2 Receptor Knockout Mice

Cardiac Hypertrophy and Microvascular Deficit in Kinin B2 Receptor Knockout Mice

ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats

B-Type Natriuretic Peptide Prevents Acute Hypertrophic Responses in the Diabetic Rat Heart

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