Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia

2011 ◽  
Vol 301 (3) ◽  
pp. H1107-H1117 ◽  
Author(s):  
Chien-Chang Chen ◽  
Yu-Jung Hsu ◽  
Tsung-Ming Lee
Keyword(s):  
Uric Acid ◽  
Ventricular Remodeling ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Endothelin 1 ◽  
Male Wistar Rats ◽  
Oxidant Production ◽  
Uricosuric Agent ◽  
Dependent Pathway ◽  
Oxonic Acid

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.

scholarly journals Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension

2009 ◽  
Vol 296 (6) ◽  
pp. H2007-H2014 ◽  
Author(s):  
Inês Falcão-Pires ◽  
Nádia Gonçalves ◽  
Tiago Henriques-Coelho ◽  
Daniel Moreira-Gonçalves ◽  
Roberto Roncon-Albuquerque ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Peak Rate ◽  
Male Wistar Rats ◽  
Neurohumoral Activation

We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats were injected with MCT (60 mg/kg sc) or vehicle ( day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 μg·kg−1·day−1 ip) or a similar volume of saline, resulting in four groups: sham ( n = 11), sham-AP ( n = 11), MCT ( n = 16), and MCT-AP ( n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 ± 38%), diameter of cardiomyocyte (40 ± 10%), myocardial fibrosis (95 ± 20%), peak systolic pressure (99 ± 22%), peak rate of ventricular pressure rise (dP/d tmax; 74 ± 24%), peak rate of ventricular pressure decline (dP/d tmin; 73 ± 19%), and time constant τ (55 ± 16%). In these animals, RV expression of apelin (−73 ± 10%) and its receptor APJ (−61 ± 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 ± 713%), angiotensinogen (191 ± 147%), endothelin-1 (RV, 497 ± 156%; and LV, 799 ± 309%), plasmatic levels of apelin (104 ± 48%), and angiotensin 1-7 (161 ± 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation.

Additive effects of combined blockade of AT1 receptor and HMG-CoA reductase on left ventricular remodeling in infarcted rats

2006 ◽  
Vol 291 (3) ◽  
pp. H1281-H1289 ◽  
Author(s):  
Tsung-Ming Lee ◽  
Mei-Shu Lin ◽  
Tsai-Fwu Chou ◽  
Nen-Chung Chang
Keyword(s):  
Myocardial Infarction ◽  
Combination Treatment ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Border Zone ◽  
Cardiomyocyte Hypertrophy ◽  
Angiotensin Receptor ◽  
Hmg Coa Reductase ◽  
Endothelin 1 ◽  
Coa Reductase

Both angiotensin receptor antagonists and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to attenuate cardiomyocyte hypertrophy after myocardial infarction. Whether combination treatment may be superior to either drug alone on cardiomyocyte hypertrophy remains unclear. After ligation of the left anterior descending artery, rats were randomized to both, one, or neither of the angiotensin receptor antagonists olmesartan (0.01, 0.1, 1, and 2 mg·kg−1·day−1) and HMG-CoA reductase inhibitor pravastatin (5 mg·kg−1·day−1) for 4 wk. Each drug, when given alone, decreased cardiomyocyte sizes isolated by enzymatic dissociation at the border zone when compared with vehicles. However, compared with either drug alone, combined olmesartan and pravastatin prevent cardiomyocyte hypertrophy to a larger extent, which was further confirmed by downregulation of the left ventricular atrial natriuretic peptide mRNA. The myocardial endothelin-1 levels at the border zone were 6.5-fold higher ( P <0.0001) in the vehicle group compared with the sham group, which can be inhibited after pravastatin administration. Combination treatment significantly attenuated cardiomyocyte hypertrophy in a dose-dependent manner, although tissue endothelin-1 levels remained stable in combination groups of different olmesartan doses. Measurements of the arrhythmic score mirrored those of cardiomyocyte hypertrophy. Dual therapy with pravastatin and olmesartan, which produced an additive reduction in cardiomyocyte hypertrophy and cardiac fibrosis after myocardial infarction through different mechanisms, decreases the propensity of the heart to arrhythmogenesis. Pravastatin administration provided favorable ventricular remodeling, probably through decreased tissue endothelin-1 level. In contrast, olmesartan-related attenuated cardiomyocyte hypertrophy is independent of endothelin-1 pathway.

scholarly journals Effect and Mechanism of Sacubitril/valsartan on Ventricular Remodeling in STZ induced Diabetic Cardiomyopathy Rats

2020 ◽  
Author(s):  
Kai Tang ◽  
Zhan Lv ◽  
Jiao Ai ◽  
Zhuang Shuai ◽  
Zongyu Li ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Protein Expression ◽  
Body Mass ◽  
Diabetic Cardiomyopathy ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Collagen Fibers ◽  
Myocardial Tissue ◽  
Tnf Α ◽  
Male Wistar Rats

Abstract Background: Diabetic cardiomyopathy (DCM) has a high incidence of heart failure and poor prognosis, so its prevention and treatment should be more active. In this study, we investigate the effect and mechanism of sacubitril/valsartan (Sac/Val) on ventricular remodeling in DCM rats, so as to provide a new idea for clinical prevention of DCM.Methods: Twenty 8-week-old male Wistar rats were randomly divided into four groups: normal rat group (NOR), DCM group, DCM+ Sac/Val group and DCM+ Perindopril (PER) group , with 5 rats in each group. The DCM rat model was established by intraperitoneal injection of 1% streptozotocin (STZ). NOR and DCM groups were gavaged with normal saline (1ml/100g/d) for 8 weeks, while Sac/Val and PER groups were gavaged with Sac/Val (60mg/kg/d) and PER (2mg/kg/d) for 8 weeks. HE and Masson staining were used to evaluate the pathological changes of myocardial tissue, the left ventricular/ body mass index was calculated to evaluate ventricular remodeling, the levels of IL-6 and TNF- α in myocardial tissue were detected by ELISA, and the protein expression of p-38 and phos-p38 was detected. Results: Compared with the NOR group, the arrangement of cardio myocytes in the DCM group was disordered and the content of collagen fibers increased. In the DCM group, the left ventricular/body mass index increased, the levels of IL-6 and TNF- α increased, and the phos-p38 protein expression increased (P＜0.01). Compared with DCM group, fewer collagen fibers were found and the degree of fibrosis was reduced in Sac/Val group and PER group. The levels of left ventricular/body mass index, IL-6, TNF- α and phos-p38 protein expression in the Sac/Val group were all lower than those in the DCM group, and the differences were statistically significant (P＜0.01).Conclusion: Sac/Val can improve ventricular remodeling in DCM, and its mechanism may be related to its anti-inflammatory effect and inhibition of p38 signaling pathway in myocardial tissue.

Interaction of high-intensity endurance exercise and nandrolone on cardiac remodeling: role of adipo-cardiac axis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Manijeh Motevalian ◽  
Siyavash Joukar ◽  
Saeed Esmaeili-Mahani ◽  
Abdollah Karimi ◽  
Yaser Masoumi-Ardakani ◽  
...  
Keyword(s):  
Endurance Exercise ◽  
High Intensity ◽  
Chronic Administration ◽  
Left Ventricular ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Α Level ◽  
Androgenic Steroids

Abstract Objectives Given the cardiac pathological remodeling following to anabolic androgenic steroids (AASs) consumption, we examined the effect of chronic administration of nandrolone decanoate with high-intensity endurance exercise on the left ventricular hypertrophy index, levels of hydroxyproline, tumor necrosis factor-alpha (TNF-α), adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) expression in rats’ hearts. Methods The male Wistar rats randomly divided to six groups included the control (CTL), exercise (Ex), nandrolone (Nan), vehicle (Arach), trained vehicle (Ex + Arach), and trained nandrolone (Ex + Nan) groups that were treated for eight weeks. Results Nandrolone consumption significantly enhanced the hypertrophy index (p<0.05) and exercise intensified this effect. It also increased the level of cardiac hydroxyproline (p<0.001), however exercise completely masked this effect. The values of TNF-α protein and AdipoR1 protein significantly increased in trained nandrolone-treated (Ex + Nan) group in comparison with CTL group (p<0.05), however, did not show significant alteration in Nan or Ex groups. High-intensity endurance exercise significantly enhanced the AdipoR2 protein (p<0.05), but, co-administration of nandrolone with exercise prevented this effect. The mRNA expression of AdipoR1 significantly reduced in the animals that received nandrolone for eight weeks and exercise recovered this effect (p<0.001). Conclusions Despite an additive effect of high-intensity endurance exercise plus nandrolone on TNF-α level, their effects on hydroxyproline and APN receptors expression is incompatible in heart of rat. It is suggests a part of beneficial regulatory role of endurance exercise against nandrolone induced heart remodeling may apply through modulation of APN system.

Effects of sulfonylureas on left ventricular mass in type 2 diabetic patients

2007 ◽  
Vol 292 (1) ◽  
pp. H608-H613 ◽  
Author(s):  
Tsung-Ming Lee ◽  
Mei-Shu Lin ◽  
Chang-Her Tsai ◽  
Chen-Ling Huang ◽  
Nen-Chung Chang
Keyword(s):  
Treated Group ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Endothelin 1 ◽  
Ventricular Mass ◽  
Lv Mass ◽  
Dependent Pathway ◽  
Type 2 Diabetic

Myocardial ATP-sensitive potassium (KATP) channels have been implicated in attenuating cardiac hypertrophy by modulating endothelin-1 concentrations. Sulfonylureas differ in their affinity for cardiac KATPchannels and therefore may vary in their effects on left ventricular (LV) mass. We sought to determine the differential effects of sulfonylureas on LV mass in type 2 diabetic patients. All patients had been taking glibenclamide for more than 3 mo before being randomized to either switch to an equipotent dose of gliclazide or continue glibenclamide. A total of consecutive 240 diabetic patients were randomized into glibenclamide, gliclazide, a combination of glibenclamide and nicorandil, or gliclazide and nicorandil for 6 mo. In the gliclazide-treated group, the LV mass index was significantly decreased compared with that in the glibenclamide-treated groups. Nicorandil administration significantly reduced LV mass in glibenclamide-treated patients compared with patients treated with glibenclamide alone. Measurements of endothelin-1 concentrations mirrored the functional status of KATPchannel. Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in endothelin-1 ( P < 0.0001). Our results show that KATPchannels may play a pathogenetic role, probably through an endothelin-1-dependent pathway, in diabetes mellitus-related ventricular hypertrophy. Patients treated with gliclazide may have a beneficial effect in attenuating ventricular mass.

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