Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy

Kompa, A.; Wang, Bing Hui; Phrommintikul, Arintaya; Ho, Pei Yi; Kelly, Darren J.; Behm, David J.; Douglas, Stephen A.; Krum, Henry

doi:10.1016/j.peptides.2010.04.026

Cited by 17 publications

(13 citation statements)

References 35 publications

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“…However, in our experiment, after three weeks, the rats developed significant cardiac hypertrophy with a lower acute (24-hour) mortality rate (8% compared with 15%) than in previous reports 3,5…”

Section: Discussioncontrasting

confidence: 71%

Changes in cardiac structure and function in a modified rat model of myocardial hypertrophy

Dai

Dong

Chen³

et al. 2016

CVJA

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SummaryAimIn this study we designed a modified method of abdominal aortic constriction (AAC) in order to establish a stable animal model of left ventricular hypertrophy (LVH). We also evaluated cardiac structure and function in rats with myocardial hypertrophy using echocardiography, and provide a theory and experimental basis for the application of drug interventions using the LVH animal model. We hope this model will provide insight into novel clinical therapies for LVH.MethodsThe abdominal aorta of male Wistar rats (80–100 g) was constricted between the branches of the coeliac and anterior mesenteric arteries, to a diameter of 0.55 mm. Echocardiography, using a linear phase array probe, combined with histology and plasma BNP concentration, was performed at three, four and six weeks post AAC.Results:The acute (24-hour) mortality rate was lower (8%) than in previous reports (15%) using this modified rat model. Compared with shams, animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), crosssectional area (CSA) of myocytes, and perivascular fibrosis; while the ejection fraction (EF), fractional shortening (FS) and cardiac output (CO) were consistently lower at each time interval. Notably, differences in these parameters between the AAC and sham groups were significant by three weeks and reached a peak at four weeks. Following AAC, plasma B-type natriuretic peptide (BNP) level was gradually elevated, compared with the sham group, between three and six weeks.ConclusionThis modified AAC model induced LVH both stably and safely by week four post surgery. Echocardiography was accurately able to assess changes in chamber dimensions and systolic properties in the rats with LVH.

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Section: Discussioncontrasting

confidence: 71%

Changes in cardiac structure and function in a modified rat model of myocardial hypertrophy

Dai

Dong

Chen³

et al. 2016

CVJA

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“…Four weeks after the induction of MI, all mice were anesthetized with isofurane, intubated and ventilated for cardiac catheterization procedures [21]. The mice were placed supine on a platform with a heating unit.…”

Section: Methodsmentioning

confidence: 99%

Cardiac-Specific Overexpression of Silent Information Regulator 1 Protects Against Heart and Kidney Deterioration in Cardiorenal Syndrome via Inhibition of Endoplasmic Reticulum Stress

Huang

Yan

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. Methods: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. Results: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-β expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. Conclusions: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.

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“…Animals were anesthetized with pentobarbitone (30 mg/kg ip) and intubated for cardiac catheterization procedures, as previously described (26). Briefly, animals were ventilated and a 2-F miniaturized combined catheter/micromanometer (model SPR838; Millar Instruments, Houston, TX) was inserted into the right common carotid artery to obtain aortic BP and then advanced into the left ventricle to obtain left ventricular pressure-volume loops.…”

Section: Cardiac Function Assessment-echocardiography and Millar Cathmentioning

confidence: 99%

Myocardial infarction impairs renal function, induces renal interstitial fibrosis, and increases renal KIM-1 expression: implications for cardiorenal syndrome

Lekawanvijit

Kompa

Zhang

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Progressive decline in renal function coexists with myocardial infarction (MI); however, little is known about its pathophysiology. This study aimed to systematically identify post-MI renal changes (functional, histological, and molecular) over time in a rat MI model and examine potential mechanisms that may underlie these changes. Rats were randomized into three groups: nonoperated, sham, and MI. Cardiac and renal function was assessed before death at 1, 4, 8, 12, and 16 wk with tissues collected for histological, protein, and gene studies. Tail-cuff blood pressure was lower in MI than sham and nonoperated animals only at 1 wk (P < 0.05). Systolic function was reduced (P < 0.0001) while heart/body weight and left ventricle/body weight were significantly greater in MI animals at all time points. Glomerular filtration rate decreased following MI at 1 and 4 wk (P < 0.05) but not at 8 and 12 wk and then deteriorated further at 16 wk (P = 0.052). Increased IL-6 gene and transforming growth factor (TGF)-β protein expression as well as macrophage infiltration in kidney cortex was detected at 1 wk (P < 0.05). Renal cortical interstitial fibrosis was significantly greater in MI animals from 4 wk, while TGF-β bioactivity (phospho-Smad2) was upregulated at all time points. The degree of fibrosis increased and was maximal at 16 wk. In addition, kidney injury molecule-1-positive staining in the tubules was more prominent in MI animals, maximal at 1 wk. In conclusion, renal impairment occurs early post-MI and is associated with hemodynamic and structural changes in the kidney possibly via activation of the Smad2 signaling pathway.

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Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy

Cited by 17 publications

References 35 publications

Changes in cardiac structure and function in a modified rat model of myocardial hypertrophy

Changes in cardiac structure and function in a modified rat model of myocardial hypertrophy

Cardiac-Specific Overexpression of Silent Information Regulator 1 Protects Against Heart and Kidney Deterioration in Cardiorenal Syndrome via Inhibition of Endoplasmic Reticulum Stress

Myocardial infarction impairs renal function, induces renal interstitial fibrosis, and increases renal KIM-1 expression: implications for cardiorenal syndrome

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