Upregulation of bradykinin B1‐receptor expression after myocardial infarction

Tschöpe, Carsten; Heringer-Walther, Silvia; Koch, Matthias; Spillmann, Frank; Wendorf, Michael; Leitner, Eszter; Schultheiss, Heinz‐Peter; Walther, Thomas

doi:10.1038/sj.bjp.0703239

Cited by 61 publications

(43 citation statements)

References 6 publications

(9 reference statements)

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“…Six hours after coronary ligation, B1R expression was first detected (35). Similar to the B2R, the up-regulation of B1R expression reached its maximum 24 h after induction of MI.…”

Section: Regulation Of the B1r After Induction Of MImentioning

confidence: 74%

Regulation of the kinin receptors after induction of myocardial infarction: a mini-review

Tschöpe

Heringer-Walther

Walther

2000

Braz J Med Biol Res

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It is well known that the responses to vasoactive kinin peptides are mediated through the activation of two receptors termed bradykinin receptor B1 (B1R) and B2 (B2R). The physiologically prominent B2R subtype has certainly been the subject of more intensive efforts in structure-function studies and physiological investigations. However, the B1R activated by a class of kinin metabolites has emerged as an important subject of investigation within the study of the kallikreinkinin system (KKS). Its inducible character under stress and tissue injury is therefore a field of major interest. Although the KKS has been associated with cardiovascular regulation since its discovery at the beginning of the last century, less is known about the B1R and B2R regulation in cardiovascular diseases like hypertension, myocardial infarction (MI) and their complications. This mini-review will summarize our findings on B1R and B2R regulation after induction of MI using a rat model. We will develop the hypothesis that differences in the expression of these receptors may be associated with a dual pathway of the KKS in the complex mechanisms of myocardial remodeling. Key wordsThe kallikrein-kinin system Kinins are biologically active peptides which exert a broad spectrum of physiological effects, including vasodilation, smooth muscle contraction and pain induction. Several kinin peptides have been identified in mammalian species: the nonapeptide bradykinin (BK) and the decapeptide Lys-bradykinin (kallidin) belong to the best investigated members of the kinin family. Kinins are formed by cleavage from precursor kininogens by kallikreins (KLK). They are rapidly degraded by several kininases, including kininase II which is identical to angiotensinconverting enzyme. Kinins exert their effect after stimulation of their cell surface receptors: BK B1 receptor (B1R) and B2 receptor (B2R). Whereas the B2R is responsive to the intact kinins, BK and kallidin, the B1R has a higher affinity for the carboxypeptidase metabolites of kinins, des-Arg 9 -BK and des-

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“…Six hours after coronary ligation, B1R expression was first detected (35). Similar to the B2R, the up-regulation of B1R expression reached its maximum 24 h after induction of MI.…”

Section: Regulation Of the B1r After Induction Of MImentioning

confidence: 74%

Regulation of the kinin receptors after induction of myocardial infarction: a mini-review

Tschöpe

Heringer-Walther

Walther

2000

Braz J Med Biol Res

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“…53 Furthermore, ACE itself can also upregulate the gene expression of both BK receptors by up to 11-22 fold, via a mechanism apparently unrelated to its enzymatic properties. 66 It was reported that in myocardial tissues of rats submitted to acute myocardial infarct there was a significant upregulation of both B 1 R and B 2 R detectable within 6 h and reaching its peak at 24 h, 57,67,68 with the B 1 R expression returning gradually to baseline in the next 3-6 days, whereas the B 2 R overexpression appears to last much longer. Thus, myocardial ischemia-whether due to Ang II-induced coronary constriction or to mechanical coronary obstruction-is associated with an upregulation of both BK receptors that would seem to be compensatory, but may also have noxious effects as well.…”

Section: B 2 R-mediated Cardioprotection Post Ischemic Injurymentioning

confidence: 99%

“…These data indicated that potentiation of BK in the absence of B 1 R is insufficient to provide full cardioprotection, despite upregulated B 2 R; however, in the setting of absent B 2 R and upregulated B 1 R, the potentiation of BK actually seems to inflict further cardiac tissue damage. 68 In view of the known proinflammatory and noxious B 1 R-mediated actions and the loss of the metabolic B 2 R-mediated properties that would enhance glucose utilization by the ischemic myocardium, it is not surprising that BK potentiation in the setting of absent B 2 R and upregulated B 1 R would exert an additional detrimental effect on the injured myocardium.…”

Section: B 2 R-mediated Cardioprotection Post Ischemic Injurymentioning

confidence: 99%

Cardioprotective properties of bradykinin: role of the B2 receptor

et al. 2010

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Following the introduction of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and ischemic heart disease, there has been increasing interest in the bradykinin-mediated aspects of ACE inhibition. Several preclinical and clinical studies have been conducted using genetically engineered animals or pharmacological agonists and antagonists of the two receptors of bradykinin, B 1 R and B 2 R. The results have mostly indicated that the B 1 R, whose expression is induced by tissue damage, seem to have mostly noxious effects, whereas the constitutively expressed B 2 R, when activated, exert mostly beneficial actions. Accumulating evidence in the recent literature suggests that the B 2 R have an important role in the process of ischemic post-conditioning that limits the ischemia/reperfusion injury of the myocardium. In this article, we describe a series of experiments conducted on mice submitted to acute myocardial infarct and treated either with ACE inhibition (which produces potentiation of bradykinin resulting in non-selective B 1 R and B 2 R activation) or with a potent and highly selective B 2 R agonist. These data suggest that this latter pharmacological approach offers functional and structural benefits and is therefore a promising cardioprotective therapeutic modality against acute ischemic events. INTRODUCTIONThe possible role of bradykinin (BK) in cardiovascular regulation has intrigued scientists for many years. A member of the kinin system discovered in the late 1920s, BK is a nonapeptide whose existence was first recognized by Roha e Silva et al. 1 from its effects on intestinal smooth muscle. Since then, several other actions of BK were described, including vascular contraction and relaxation, participation in the process of inflammatory reactions, interaction with central and peripheral neural structures, stimulation of synthesis and release of various vasoactive substances, enhanced insulin-dependent glucose transport and utilization, etc.Circulatory homeostasis is the result of a constant equilibrium between vasoconstrictors (e.g., pressor neurohormonal factors like angiotensin II, catecholamines, vasopressin, endothelin) and vasodilators (like kinins, prostaglandins, NO, etc.). Bradykinin, a tissue hormone that regulates the regional blood flows of vital organs, is an important member of the latter group. 2 The role of BK in cardiovascular regulation under physiological and pathological conditions attracted the interest of clinicians with the advent of angiotensinconverting enzyme (ACE) inhibitors, which in the last two decades have become standard therapy for hypertension, ischemic heart disease and heart failure. 3 In recent years the work of many investigators has produced a lot of new information regarding the role of kinins in the pathophysiology of hypertension and the prevention of its end-organ complications.

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“…For example, administration of an ACEI shortly after acute myocardial infarction reduced the incidence of death or development of severe congestive heart failure (3,4). Acute myocardial infarction also induces B 1 receptor expression (39). The induction and activation of the B 1 receptor could prove advantageous under various stressful conditions, ranging from infection to cardiovascular disorders (15).…”

Section: Ace Inhibitors Activation Of Bk B 1 Receptormentioning

confidence: 99%