Effects of long-term angiotensin II AT1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats

Richer, Christine; Fornès, Paul; Cazaubon, Catherine; Domergue, Valérie; Nisato, Dino; Giudicelli, Jean‐François

doi:10.1016/s0008-6363(98)00227-2

Cited by 59 publications

(40 citation statements)

References 30 publications

(14 reference statements)

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“…This first conclusion may be strengthened by the fact that early shortterm treatment with Los significantly reduced neutrophils, RAM 11-positive macrophages, and CD45 RO-positive lymphocytes at 4 days post-MI, whereas long-term therapy delayed the healing process, as determined by the persistency of these inflammatory cells and the reduction of collagen content at 35 days. In contrast with results reported in other species (16,21,27,31,37), long-term therapy increased the dilation and reduced the scar collagen content at 35 and 56 days post-MI. In animals treated with Los from the beginning of MI, we also found a significant reduction in the scar thickness at 35 days.…”

Section: Discussioncontrasting

confidence: 99%

Effect of early versus late AT₁ receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits

Gónzalez¹,

Seropián²,

Krieger³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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González GE, Seropian IM, Krieger ML, Palleiro J, Lopez Verrilli MA, Gironacci MM, Cavallero S, Wilensky L, Tomasi VH, Gelpi RJ, Morales C. Effect of early versus late AT1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits. Am J Physiol Heart Circ Physiol 297: H375-H386, 2009. First published May 8, 2009 doi:10.1152/ajpheart.00498.2007.-To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late (day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days (P Ͻ 0.05). ANG II levels increased (P Ͻ 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right (P Ͻ 0.05). This shift was even more pronounced in long-term-treated groups (P Ͻ 0.05). Contractility decreased (P Ͻ 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 Ϯ 0.05 to 3.05 Ϯ 0.02 cells/high-power field (HPF; P Ͻ 0.05) and CD45 RO-positive lymphocytes from 2.23 Ϯ 0.05 to 1.48 Ϯ 0.01 cells/HPF (P Ͻ 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 Ϯ 2.35% and MI ϩ losartan: 57.50 Ϯ 2.48, P Ͻ 0.05), determined the persistency of RAM 11-positive macrophages (3.02 Ϯ 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 Ϯ 0.58 cells/HPF, P Ͻ 0.05 vs. MI), and reduced the scar thinning ratio at 35 days (P Ͻ 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.angiotensin II type 1 receptor blockers MYOCARDIAL INFARCTION (MI) leads to global structural alterations that involve infarcted as well as noninfarcted areas in a process collectively known as ventricular remodeling (26). The initial phase of remodeling, which starts in the acute phase of the MI, is associated with geometric changes and dilation of the MI zone, as a consequence of injured wall thinning (14, 26). Shortly afterward, this dilation may progress to the whole ventricle, and...

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Section: Discussioncontrasting

confidence: 99%

Effect of early versus late AT₁ receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits

Gónzalez¹,

Seropián²,

Krieger³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Irbesartan treatment was started 2 weeks after ovariectomy at 50 mg⅐kg -1 ⅐d -1 by adding the drug to the drinking water. 20 The rats were killed by decapitation. Animal experiments were performed in accordance with the German animal protection law.…”

Section: Animalsmentioning

confidence: 99%

Endothelial Dysfunction and Oxidative Stress During Estrogen Deficiency in Spontaneously Hypertensive Rats

et al. 2001

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Background-Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT 1 ) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT 1 receptor regulation during estrogen deficiency, ovariectomized spontaneously hypertensive rats (SHR) were investigated in comparison with sham-operated animals and with ovariectomized rats receiving estrogen replacement therapy with 17␤-estradiol. Methods and Results-Arterial blood pressure was similar in all 3 groups investigated. Five weeks after ovariectomy, endothelial dysfunction in aortic rings was observed, which was reversed by estrogen replacement therapy. Estrogen deficiency led to an enhanced vasoconstriction by angiotensin II. Vascular superoxide production was significantly increased compared with that in sham-operated rats, as measured by lucigenin chemiluminescence assays. Estrogen substitution normalized the production of free radicals in the vessel wall. Vascular AT 1 receptor expression was significantly upregulated by estrogen deficiency, as shown by quantitative reverse transcription-polymerase chain reaction, whereas endothelial NO synthase mRNA expression and NO release were unchanged. Five-week treatment of the animals with the AT 1 receptor antagonist irbesartan prevented endothelial dysfunction in ovariectomized rats and normalized the vascular production of free radicals. Conclusions-In

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“…5,18 The improvement of LV function by losartan is probably by reduction of preload, afterload and wall stress and improvement of the oxygenation and systolic function of cardiomyocytes. 22 …”

Section: Effect Of Carvedilol and Losartan Alone And In Combination Omentioning

confidence: 99%

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

Yang

Tang

Ruan

et al. 2003

Circ J

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t is well known that left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) plays a very important role in progressive left ventricular (LV) dysfunction and subsequent heart failure. It is characterized by infarct expansion, hypertrophy of the noninfarcted myocardium and alteration of LV geometry, and manifests as progressive LV dilatation. Experimental studies have shown that angiotensin II type I (AT1) receptor antagonists, such as losartan, is beneficial in attenuating post-infarction LVRM. 1-4 Carvedilol, a third-generationblocker, is a unique, multiaction drug with non-selectiveblockade, 1-blockade and antioxidant effects. Clinical studies have shown that carvedilol is beneficial in preventing LVRM in patients with ischemic heart failure. 5,6 Therefore, we hypothesized that carvedilol should be effective, Circulation Journal Vol.67, February 2003 and its combination with losartan should be superior, in preventing post-infarction LVRM. So, the purpose of this study was to compare the effects of carvedilol and losartan alone and in combination on LVRM after AMI in rats. Methods Experimental Rats and GroupsAMI as induced by ligating the left coronary artery in 133 female Sprague-Dawley (SD) rats (body weight: 200-250 g). At 24 h after the operation, the 100 surviving rats were randomized to 4 groups: (1) AMI controls (n=25), (2) carvedilol (1 mg·kg -1 ·d -1 , n=25), (3) losartan (3 mg·kg -1 ·d -1 , n=25), and (4) carvedilol (1 mg·kg -1 ·d -1 ) + losartan (3 mg · kg -1 · d -1 ) (combination, n=25) groups. Sham-operated rats (n=17) were randomly selected before the AMI operation. MethodsAMI was conducted by a method previously reported by Olivetti et al. 7 After anaesthesia with ketamine (30 mg/kg) and diazepam (5 mg/kg), and then a thoracotomy, the left coronary artery of each rat was ligated using a 6-0 prolene suture, which induced an anterior myocardial infarction. In It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female SpragueDawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg·kg -1 · day -1 ) (n=25), (3) losartan (Los, 3 mg·kg -1 ·day -1 ) (n=25), and (4) Car (1 mg·kg -1 ·day -1 ) + Los (3 mg·kg -1 · day -1 ) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13)

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Effects of long-term angiotensin II AT1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats

Cited by 59 publications

References 30 publications

Effect of early versus late AT₁ receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits

Effect of early versus late AT₁ receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits

Endothelial Dysfunction and Oxidative Stress During Estrogen Deficiency in Spontaneously Hypertensive Rats

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

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