Involvement of the Renin–Angiotensin System in Ischemic Damage and Reperfusion Arrhythmias in the Isolated Perfused Rat Heart

Fleetwood, G.; Boutinet, S.; Meier, Matthias; Wood, J. M.

doi:10.1097/00005344-199103000-00001

Cited by 61 publications

(28 citation statements)

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“…This demonstrates that ischemia/reperfusion promotes the release of active renin from cardiac mast cells, thus initiating local Ang II formation and an AT 1 receptor-mediated increase in the magnitude of NE release and the severity of arrhythmias. It is conceivable that Ang II contributed to reperfusion arrhythmias not only by facilitating NE release (15,(34)(35)(36) but also by its direct arrhythmogenic action (37,38). Further, although mast cell stabilization, renin inhibition, and AT 1 receptor blockade inhibited NE release, this inhibition was not complete.…”

Section: Figurementioning

confidence: 99%

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion

Mackins

Kano²,

Seyedi³

et al. 2006

Journal of Clinical Investigation

187

220

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Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT 1 ) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT 1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

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Section: Figurementioning

confidence: 99%

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion

Mackins

Kano²,

Seyedi³

et al. 2006

Journal of Clinical Investigation

187

220

View full text Add to dashboard Cite

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“…Another possibility for reducing mortality in the group treated is that ACE inhibition prevented the early deaths due to the arrhythmias triggered by myocardial ischemia. Several studies [25][26][27] have reported that, in that model, the coronary reserve is decreased, angiotensin II worsens and ACEIs protect against arrhythmias of reperfusion after transient myocardial ischemia in rats 26,28 , and the myocardial tissue RAAS activity is exacerbated 12,21,29 . Before treatment, the SG animals had a 34.7% greater LVMI than that of the CG animals.…”

Section: Discussionmentioning

confidence: 99%

Efeitos da inibição prolongada da enzima de conversão da angiotensina sobre as características morfológicas e funcionais da hipertrofia ventricular esquerda em ratos com sobrecarga pressórica persistente

Bregagnollo¹,

Okoshi²,

Bregagnollo³

et al. 2005

Arq. Bras. Cardiol.

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Left ventricular hypertrophy (LVH) is an adaptive response of the heart to sustained work overload. Data in the literature 1 have shown that the load conditions and neurohumoral systems, among which the renin-angiotensin-aldosterone system (RAAS) stands out, modulate the characteristics of left ventricular hypertrophy that develop in the presence of chronic pressure overload. Clinical studies 2,3 have shown that angiotensin-converting enzyme inhibitors (ACEI) improve the survival of patients with heart failure, delay heart decompensation in patients with asymptomatic left ventricular dysfunction, and attenuate the progression of left ventricular dilation and dysfunction after myocardial infarction. Experimental studies [4][5][6] have shown that ACEIs attenuate ventricular remodeling, improve survival, and delay the progression of left ventricular dysfunction in rats with myocardial infarction and hamsters with cardiomyopathy. Angiotensin-converting enzyme inhibitors have also been proved to decrease left ventricular hypertrophy in human beings 7 and in experimental animals with chronic pressure overload 8,9 . The favorable effects of ACEI on survival and regression of left ventricular hypertrophy in heart failure and arterial hypertension are frequently attributed to interference with the RAAS, resulting in a reduction in blood pressure and peripheral vascular resistance with a consequent reduction in cardiac overload 10 . However, several studies [10][11][12] have reported that the angiotensin-converting enzyme (ACE) and the myocardial tissue RAAS are activated in animal models of heart failure and cardiac hypertrophy. Although the efficacy of the ACEI in prolonging survival, delaying the development of ventricular dysfunction, and reversing cardiac hypertrophy is widely recognized, it has been difficult to dissociate the hemodynamic effects of those agents on systemic blood pressure from the effects of the myocardial tissue ACE blockade. Therefore, the use of ACEI in arterial hypertension, acute myocardial infarction, and cardiomyopathy is clearly justified, because those drugs block RAAS activity, reduce cardiac load, and reverse left ventricular hypertrophy. The validity of that strategy is controversial when the increase in cardiac load is relatively fixed, as in the case of aortic valvular stenosis. In that circumstance, the reduction in left ventricular hypertrophy may be seen as a loss of the adaptive mechanism that can result in maladjustment of the afterload, and dilation and impairment of left ventricular function. Alternati- Original Article Effects of the Prolonged Inhibition of the Angiotensin-Converting Enzyme on the Morphological and Functional Characteristics of Left Ventricular Hypertrophy in Rats with ObjectiveTo assess the effects of lisinopril (L) on mortality (M) rate and congestive heart failure (CHF), and the characteristics of geometrical myocardial remodeling and left ventricular function in rats with supravalvular aortic stenosis (SAS). MethodsSome Wistar rats underwent SAS or the sim...

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“…Pretreatment of rats with captopril It is well known that ACE activity in the myocardium and Ang-II levels in plasma and cardiac tissues increase after acute myocardial ischemia. [1][2][3][4] Increased ACE activity also leads to increased breakdown of bradykinin. These neuro-hormonal changes may exacerbate myocardial ischemia and cause expansion of the infarcted area.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] ACE gene deletion polymorphism, which relates to a high plasma level of ACE, has been reported to be associated with a high risk of myocardial infarction and sudden death. [5][6][7][8] Many studies show that ACE activity and angiotensin-II (Ang-II) levels increase in plasma after acute myocardial ischemia, which may lead to exacerbation of myocardial ischemia, cardiac dysfunction and expansion of infarct size.…”

Section: Introductionmentioning

confidence: 99%

Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

Chen

Mohuczy

et al. 2001

Gene Ther

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Angiotensin-converting enzyme (ACE) activity in the myocardium and angiotensin-II (Ang-II) levels in plasma increase after myocardial ischemia, which lead to exacerbation of myocardial injury and cardiac dysfunction. We examined the protective role of novel antisense-oligodeoxynucleotide (AS-ODN) directed at ACE mRNA in myocardial ischemic injury. Sprague-Dawley rats were treated with ACE-AS-ODN (200 g per rat, n = 8, i.v.) or inverted-ODN (IN-ODN, 200 g per rat, n = 8, i.v.), given with 600 g per rat of liposome DOTAP/DOPE. Hearts from AS-ODN-or IN-ODNtreated rats were excised, perfused in vitro, and subjected to 25 min of global ischemia followed by 30 min of reperfusion. Parallel groups of rats were given ACE inhibitor captopril (5 mg/kg, n = 8) or saline (n = 8) before excising the hearts. Ischemia/reperfusion resulted in myocardial dysfunction (increase in coronary perfusion pressure and LV end-diastolic pressure and a decrease in developed LV pressure) in the saline-treated rats. Myocardial dysfunction was associa-

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Involvement of the Renin–Angiotensin System in Ischemic Damage and Reperfusion Arrhythmias in the Isolated Perfused Rat Heart

Cited by 61 publications

References 0 publications

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion

Efeitos da inibição prolongada da enzima de conversão da angiotensina sobre as características morfológicas e funcionais da hipertrofia ventricular esquerda em ratos com sobrecarga pressórica persistente

Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

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