Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Prevents Oxidative Stress in Uremic Rats

Michea, Luis; Villagrán, Andrea; Urzúa, Álvaro; Kuntsmann, Sonia; Venegas, Pía; Carrasco, Loreto; González, Magdalena; Marusic, Elisa T.

doi:10.1161/hypertensionaha.107.109645

Cited by 52 publications

(45 citation statements)

References 43 publications

(48 reference statements)

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“…Upregulation of renal renin-angiotensin-aldosterone system was also shown in rats with partial nephrectomy in our present study similarly to findings of other research groups (25,33,41). In our present study, increased plasma ANG II levels together with echocardiographic data suggest the development of a minimal left ventricular hypertrophy at week 30 in uremic animals.…”

Section: Discussionsupporting

confidence: 92%

“…Additionally, plasma ANG II level, which is an indirect marker of hypertension and left ventricular hypertrophy (20,27,28,43,58), was also higher in uremic rats. These results together with literature data (1,33,38,41) suggest the development of a minimal left ventricular hypertrophy in uremic animals at week 30 in our present study. In this model, we have found here that ischemic preconditioning is still effective in prolonged uremic condition.…”

Section: Discussionsupporting

confidence: 91%

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Preconditioning protects the heart in a prolonged uremic condition

Kocsis

Sárközy

Bencsik

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Metabolic diseases such as hyperlipidemia and diabetes attenuate the cardioprotective effect of ischemic preconditioning. In the present study, we examined whether another metabolic disease, prolonged uremia, affects ischemia/reperfusion injury and cardioprotection by ischemic preconditioning. Uremia was induced by partial nephrectomy in male Wistar rats. The development of uremia was verified 29 wk after surgery. Transthoracic echocardiography was performed to monitor cardiac function. At week 30, hearts of nephrectomized and sham-operated rats were isolated and subjected to a 30-min coronary occlusion followed by 120 min reperfusion with or without preceding preconditioning induced by three intermittent cycles of brief ischemia and reperfusion. In nephrectomized rats, plasma uric acid, carbamide, and creatinine as well as urine protein levels were increased as compared with shamoperated controls. Systolic anterior and septal wall thicknesses were increased in nephrectomized rats, suggesting the development of a minimal cardiac hypertrophy. Ejection fraction was decreased and isovolumic relaxation time was shortened in nephrectomized rats demonstrating a mild systolic and diastolic dysfunction. Infarct size was not affected significantly by nephrectomy itself. Ischemic preconditioning significantly decreased infarct size from 24.8 Ϯ 5.2% to 6.6 Ϯ 1.3% in the sham-operated group and also in the uremic group from 35.4 Ϯ 9.5% to 11.9 Ϯ 3.1% of the area at risk. Plasma ANG II and nitrotyrosine were significantly increased in the uremic rats. We conclude that although prolonged experimental uremia leads to severe metabolic changes and the development of a mild myocardial dysfunction, the cardioprotective effect of ischemic preconditioning is still preserved. chronic renal failure; myocardium; ischemic preconditioning; infarct size; myocardial function ISCHEMIC PRECONDITIONING IS a well-characterized endogenous adaptive response of the myocardium in which brief cycles of ischemia markedly enhance the ability of the heart to withstand a subsequent ischemic injury (15). Although preconditioning confers remarkable cardioprotection in a variety of species (15, 44), including humans (21, 49, 55), we and others have shown that its effectiveness is attenuated by some risk factors and comorbidities such as metabolic diseases including hyperlipidemia (14 -16) and diabetes (35, 54) both in animal models and humans (15).

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Preconditioning protects the heart in a prolonged uremic condition

Kocsis

Sárközy

Bencsik

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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show abstract

“…A key feature of the uremic cardiac phenotype is the presence of LV hypertrophy [38] [39]. In this context, intermyocyte fibrosis and capillary rarefaction are amplified thereby bringing myocytes closer to the brink of ischemia (due to poor oxygen delivery, reduced capillary density and greater oxygen diffusion distance).…”

Section: Discussionmentioning

confidence: 99%

Ischemic Tolerance in Uremic Rabbits

Kingma¹,

Sénéchal²,

Rouleau³

et al. 2015

WJCD

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Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities; we tested whether experimentally induced prolonged uremia exacerbated myocardial necrosis in a rabbit preparation of ischemia-reperfusion injury. In addition, we examined if treatment with an angiotensin converting enzyme inhibitor (Enalapril, ENA, 3 mg/Kg, IV) could reduce post-ischemic myocardial damage. Methods: Prolonged uremia was induced by a two-stage subtotal nephrectomy and confirmed by marked increases in serum creatinine and urea levels; after 5 weeks, four groups of rabbits were exposed to 45-min acute coronary occlusion followed by 180-min reperfusion. In treated animals, ENA was administered 5-min before onset of coronary reperfusion. All data from uremic animals were compared with time-matched controls. Results: Cardiac hemodynamics was similar for all groups during the development of kidney failure; heart rate in uremic rabbits was significantly lower for the duration of ischemia-reperfusion. In this animal model, the absence of coronary collateral circulation provides a stable ischemic substrate for evaluation of cellular necrosis. Infarct size (expressed as percent risk zone size) was: control, 48 ± 16; uremia, 36 ± 5; control + ENA, 51 ± 19; and uremia + ENA, 41 ± 16; risk zone size was similar for all animals. Conclusion: The present findings are inconsistent with the view that post-ischemic cardiac injury is greater in animals with pre-existent uremia. In addition, we were unable to show a significant beneficial effect with an angiotensin converting enzyme inhibitor on infarct size in either control or uremic rabbits. It remains to be proven in animal models with comorbidities such as manifest kidney disease that ischemic tolerance can be substantially reduced by either pharmacologic or non-pharmacologic interventions.

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“…Además, se demostró una correlación positiva entre la concentración plasmática de algunos marcadores de dichos procesos y la concentración de aldosterona 15 . Estudios experimentales han señalado que los ARM son capaces de revertir los efectos deletéreos de aldosterona a nivel cardiaco disminuyendo significativamente la generación de especies reactivas de oxígeno, procesos inflamatorios y el remodelamiento de la matriz extracelular [16][17][18] .…”

Section: Arm En Insuficiencia Cardiacaunclassified

“…Estudios experimentales muestran que el tratamiento con ARM es capaz de disminuir la fibrosis auricular, la dilatación auricular y la capacidad de inducción de arritmias auriculares [47][48][49] . Estos datos han sido corroborados en parte por ensayos clí-nicos realizados en pacientes con IC que demuestran una menor tendencia a desarrollar FA y una disminución significativa del volumen auricular al ser tratados con ARM 19,22,50 .…”

Section: Arm En Fibrilación Auricularunclassified