Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist.

Benetos, A; Gavras, Haralambos; Stewart, John M.; Vavrek, Raymond J.; Hatinoglou, S; Gavras, Irène

doi:10.1161/01.hyp.8.11.971

Cited by 110 publications

(30 citation statements)

References 17 publications

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“…12 In earlier years this was accomplished mainly via use of peptide analogs with agonistic and antagonistic properties. It has generally been accepted that all the physiologically significant hemodynamic and metabolic actions of bradykinin are exerted via activation of the constitutive B 2 R. Indeed, acute and chronic infusion of BK antibodies 13 or selective B 2 R antagonists in animals 14,15 and humans 16 was shown to partly reverse the antihypertensive effect of ACE inhibitors; to prevent the cardioprotective action of ACE inhibition in animals submitted to cardiac ischemia/reperfusion injury; 17,18 and to inhibit the amelioration of insulin-dependent glucose transport by ACE inhibitors. 19,20 On the contrary, the B 1 R is believed to be mostly unexpressed under normal conditions, but is highly inducible by lipopolysaccharides, bacterial toxins and inflammatory mediators resulting from tissue injury.…”

Section: Bradykinin Receptorsmentioning

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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Section: Bradykinin Receptorsmentioning

confidence: 99%

Cardioprotective properties of bradykinin: role of the B2 receptor

et al. 2010

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“…1 -4 Additional renal actions of BK-(l-9) include the production of a diuresis and natriuresis. 5 " 8 Evidence that endogenous bradykinin peptides influence blood pressure and renal function includes the hypertensive effect of bradykinin antagonists in normotensive 9 - 12 and hypertensive 1314 rats and the decrease in renal blood flow and glomerular filtration rate in response to aprotinin (a nonspecific serine protease inhibitor that inhibits renal kallikrein) and bradykinin antagonists.uu.is-n Endogenous bradykinin peptides may also participate in the antihypertensive and renal effects of inhibitors of angiotensin converting enzyme (ACE) (kininase II, dipeptidyl carboxypeptidase, peptidyldipeptide hydrolase; EC 3.4.15.1) and neutral metalloendopeptidase-24.11 (EC 3.4.24.11,EP 24.11). '-> 8 - 19 Intravenous administration of bradykinin antagonists or kinin antibodies partially reverses the hypotensive effect of ACE inhibition in rats - 2021 and also partially reverses the effects of ACE inhibitors on renal papillary blood flow, urine flow, and sodium excretion.…”

Section: T He Nonapeptide Bradykinin [Bradykinin-(l-9)mentioning

confidence: 99%

“…82130 " 40 To investigate the role of bradykinin peptides in normal renal physiology and in hypertensive states, we developed a highly sensitive amino (N)-terminal-directed radioimmunoassay (RIA) that, with high performance liquid chromatography (HPLC), enables the measurement of bradykinin-(l-7) [BK-(l-7)], BK- (1)(2)(3)(4)(5)(6)(7)(8), and BK-(l-9). In addition, a carboxy (C)-terminaldirected RIA was applied to the measurement of BK-(1-9), bradykinin-(2-9) [BK-(2-9)], bradykinin- (3)(4)(5)(6)(7)(8)(9) [BK-(3-9)], bradykinin-(4-9) [BK-(4-9)], Ile,Ser-BK, and Met,Ile,Ser-BK. We applied both RIAs to the characterization of all eight peptides in rat kidney and blood and also applied the N-terminal-directed RIA to the measurement of bradykinin peptides in heart, aorta, brown adipose tissue, adrenal, lung, and brain.…”

mentioning

confidence: 99%

Bradykinin peptides in kidney, blood, and other tissues of the rat.

1993

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The bradykinin peptide system is a tissue-based system with potent cardiovascular and renal effects. To investigate the regulation of this system, we developed a highly sensitive amino terminal-directed radioimmunoassay that, with high performance liquid chromatography, enables the measurement of bradykinin-(l-7), bradykinin-(l-8), and bradykinin-(l-9). Together with a carboxy terminal-directed radioimmunoassay, we characterized bradykinin peptides in rat kidney and blood. The predominant bradykinin peptides in kidney were bradykinin-(l-9) (-100 fmol/g wet weight of tissue) and bradykinin-(1-7) (-70 fmol/g), with low levels of bradykinin-(l-8) (-8 fmol/g) and bradykinin-(4-9) (-12 fmol/g) detectable; bradykinin-(2-9) and bradykinin-(3-9) were below the limits of detection. In blood, the levels of bradykinin-(l-9) were very low (-2 fmol/ml), and other bradykinin peptides were below the limits of detection. Ue,Ser-bradykinin and Met,Ile,Ser-bradykinin were below the limits of detection in both kidney and blood, indicating that T-kininogen makes no detectable contribution to renal or circulating bradykinin peptides. Administration of the angiotensin converting enzyme inhibitor perindopril was associated with an approximate twofold increase in renal levels of bradykinin-(l-8) and bradykinin-(1-9) and a decrease in the bradykinin-(l-7)/bradykinin-(l-9) ratio. The amino terminal-directed radioimmunoassay was also applied to heart, aorta, brown adipose tissue, adrenal, lung, and brain. For these tissues, bradykinin-(l-7) and bradykinin-(l-9) were of similar abundance (16-340 fmol/g), with lower levels of bradykinin-(l-8). These studies demonstrate that tissue levels of bradykinin peptides are much higher than circulating levels, consistent with their formation at a local tissue site. Of peptides derived from K-kininogen, bradykinin-(l-9) is the predominant bioactive peptide in all tissues, and a major pathway of bradykinin-(l-9) metabolism involves the formation of bradykinin-(l-7). In kidney, angiotensin converting enzyme plays an important role in bradykinin-(l-9) metabolism, and increased bradykinin-(l-9) and bradykinin-(l-8) levels may mediate in part the renal effects of converting enzyme inhibition. BK-(l-9)] has important actions on blood vessels, the heart, and kidney. By far the most important hemodynamic effect of BK-(l-9) in vivo is the hypotensive vasodilation produced by stimulation of endothelial B 2 receptors of arteries and arterioles, with subsequent endothelial release of nitric oxide and prostaglandins.1 -4 Additional renal actions of BK-(l-9) include the production of a diuresis and natriuresis. 5 " 8 Evidence that endogenous bradykinin peptides influence blood pressure and renal function includes the hypertensive effect of bradykinin antagonists in normotensive 9 -12 and hypertensive 1314 rats and the decrease in renal blood flow and glomerular filtration rate in response to aprotinin (a nonspecific serine protease inhibitor that inhibits renal kallikrein) and bradykinin antagonists.uu.is-n En...

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“…It is noteworthy that the reduction in blood pressure of renovascular, hypertensive rats by enalapril is significantly blocked by the infusion of a BK antagonist, whereas no effect is observable when the pressure decrease is induced by saralasin or nitroprusside. 9 There have been several demonstrations that BK releases cyclooxygenase metabolites from various tissues. 10 In the normal dog, the hypotensive effects of captopril and BK are sig-nificantry reduced by indomethacin, thus suggesting that the acute hypotensive effect of captopril in the dog might result from the local release of prostacyclin, stimulated by increased plasma BK levels.…”

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confidence: 99%

Hypotensive effect of captopril. Role of bradykinin and prostaglandinlike substances.

1990

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T here is considerable evidence in support of a mechanism in addition to that through which inhibition of angiotensin II generation in the blood accounts for the antihypertensive action of the various converting enzyme inhibitors. In brief, essential hypertension and several experimental models of hypertension not dependent on the renin-angiotensin system are effectively controlled by captopril 1 -3 ; inhibition of plasma angiotensin converting enzyme does not always correlate with its hypotensive effect. -6Kinin antibodies are known to block the increases in uteroplacental blood flow and plasma prostaglandin E 2 induced by converting enzyme inhibitors in pregnant, nephrectomized rabbits. 7 -8 Because the same enzyme is responsible for angiotensin conversion and bradykinin (BK) inactivation, increased BK levels might partially explain the hypotensive activity of the converting enzyme inhibitors. It is noteworthy that the reduction in blood pressure of renovascular, hypertensive rats by enalapril is significantly blocked by the infusion of a BK antagonist, whereas no effect is observable when the pressure decrease is induced by saralasin or nitroprusside.9 There have been several demonstrations that BK releases cyclooxygenase metabolites from various tissues. 10 In the normal dog, the hypotensive effects of captopril and BK are sig- nificantry reduced by indomethacin, thus suggesting that the acute hypotensive effect of captopril in the dog might result from the local release of prostacyclin, stimulated by increased plasma BK levels. 11 In the present study, we reinvestigate the blockade of the hypotensive effect of captopril by indomethacin and the relation with plasma BK levels, measured by the blood-bathed bioassay technique of Vane.12 The presence of BK in the circulating blood was confirmed by blocking the response of the assay tissues with a specific BK receptor antagonist, L-349b.

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Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist.

Cited by 110 publications

References 17 publications

Cardioprotective properties of bradykinin: role of the B2 receptor

Cardioprotective properties of bradykinin: role of the B2 receptor

Bradykinin peptides in kidney, blood, and other tissues of the rat.

Hypotensive effect of captopril. Role of bradykinin and prostaglandinlike substances.

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