Captopril prevents vascular and fibrotic changes but not cardiac hypertrophy in aortic-banded rats

1996 ◽  
Vol 271 (3) ◽  
pp. H906-H913 ◽  
Author(s):  
C. P. Regan ◽  
P. G. Anderson ◽  
S. P. Bishop ◽  
K. H. Berecek
Keyword(s):  
Cardiac Hypertrophy ◽  
Coronary Vessels ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vessel Morphology ◽  
Sprague Dawley Rats ◽  
Quantitative Image

To determine the role of the renin-angiotensin system (RAS) on cardiovascular remodeling in a pressure overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male, Sprague-Dawley rats. Rats were left untreated (AB) or given captopril (Cap, 400 mg/l) (AB-Cap). Sham-operated controls were either left untreated (S) or given Cap (S-Cap). After 4 wk, rats were catheterized, and carotid and femoral mean arterial pressures (CMAP and FMAP in mmHg, respectively) were recorded. Hearts were isolated, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for vessel morphology. Changes in coronary artery medical thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Cap than S or S-Cap rats (P < 0.05). There was no difference in FMAP in AB vs. S rats, but AB-Cap and S-Cap had lower FMAP values than S rats. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Cap rats compared with S and S-Cap rats (P < 0.05). MCR of AB was greater than S and S-Cap rats. MCR of AB-Cap rats was significantly greater than S and S-Cap rats but was significantly less than AB rats. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Cap, S, and S-Cap rats. Similarly, the increase in perivascular fibrosis was greatest in AB rats, and there was no difference among AB-Cap, S, and S-Cap rats. These data suggest that the RAS, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure overload hypertrophy.

Pressure-independent effects of AT1-receptor antagonism on cardiovascular remodeling in aortic-banded rats

1997 ◽  
Vol 272 (5) ◽  
pp. H2131-H2138 ◽  
Author(s):  
C. P. Regan ◽  
P. G. Anderson ◽  
S. P. Bishop ◽  
K. H. Berecek
Keyword(s):  
Angiotensin Ii ◽  
Coronary Vessels ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Cardiovascular Remodeling ◽  
Pressure Independent ◽  
Independent Effects

To determine the role of angiotensin II-receptor blockade on cardiovascular remodeling in a pressure-overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male Sprague-Dawley rats. Aortic-banded (AB) rats were left untreated or were losartan (Los; 250 mg/l) treated (AB-Los). Sham-operated (S) controls were either left untreated or treated with Los (S-Los). After 4 wk, rats were catheterized for measurement of mean arterial pressures [carotid (CMAP) and femoral (FMAP), in mmHg]. Hearts were perfused on a modified Langendorff system, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for morphology. Changes in coronary artery medial thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Los than in S or S-Los (P < 0.05). There was no difference in FMAP in AB vs. S, but AB-Los and S-Los had lower FMAPs than S. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Los compared with S and S-Los (P < 0.05). MCR of AB was greater than S and S-Los. MCR of AB-Los was significantly lower than AB and was not significantly different from S and S-Los. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Los, S, and S-Los. Similarly, the increase in perivascular fibrosis was greatest in AB, and there was no difference among AB-Los, S, and S-Los. These data suggest that angiotensin II, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure-overload hypertrophy.

Elucidation of the mechanism of action of pinitol against pressure overload–induced cardiac hypertrophy and fibrosis in an animal model of aortic stenosis

2021 ◽  
Vol 85 (3) ◽  
pp. 643-655
Author(s):  
Xiaojing Hu ◽  
Yuanyuan Zhu ◽  
Xiaoyan L V ◽  
Zhanbin Feng
Keyword(s):  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Abdominal Aortic ◽  
Sprague Dawley Rats ◽  
Tnf Α

ABSTRACT The long-term imposition of pressure overload on the cardiac tissue causes left ventricular hypertrophy (LVH) and cardiac fibrosis. Pinitol has been reported to possess antioxidant potential. The aim was to evaluate the efficacy of pinitol against pressure overload–induced cardiac hypertrophy and fibrosis in the aortic stenosis (AS) rat model. Cardiac hypertrophy was produced in Sprague-Dawley rats by abdominal aortic constriction and treated with lisinopril (15 mg/kg) or pinitol (5, 10, and 20 mg/kg). Pressure overload–induced alterations in hemodynamic and left ventricular function tests, cardiac SOD, GSH, MDA, NO, Na-K-ATPase, and mitochondrial complex enzyme levels were significantly attenuated by pinitol. The upregulated mRNA expressions of cardiac ANP, BNP, cTn-I, TNF-α, IL-1β, IL-6, Bax, Caspase-3, collagen-I, and cardiac apoptosis were markedly downregulated by pinitol. In conclusion, pinitol ameliorated pressure overload–induced LVH and fibrosis via its anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic potential in experimental AS.

scholarly journals A Reduction in ADAM17 Expression Is Involved in the Protective Effect of the PPAR-α Activator Fenofibrate on Pressure Overload-Induced Cardiac Hypertrophy

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Si-Yu Zeng ◽  
Hui-Qin Lu ◽  
Qiu-Jiang Yan ◽  
Jian Zou
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Wall Thickness ◽  
Protective Action ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
Protein Levels

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has not been completely determined. Our previous study indicated that a disintegrin and metalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac hypertrophy. This study aimed to determine whether ADAM17 is involved in the protective action of fenofibrate against cardiac hypertrophy. Abdominal artery constriction- (AAC-) induced hypertensive rats were used to observe the effects of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary cardiomyocytes were pretreated with fenofibrate (10 μM) for 1 hour before being stimulated with angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels in left ventricle in AAC-induced hypertensive rats. Similarly, in vitro experiments showed that fenofibrate significantly attenuated angiotensin II-induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in ADAM17 expression is associated with the protective action of PPAR-α agonists against pressure overload-induced cardiac hypertrophy.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

Altered renal dopamine receptors during development of cardiac hypertrophy

1992 ◽  
Vol 262 (5) ◽  
pp. E569-E573
Author(s):  
P. K. Ganguly ◽  
K. Mukherjee ◽  
Y. Chen
Keyword(s):  
Cardiac Hypertrophy ◽  
Dopamine Receptors ◽  
Pressure Overload ◽  
Total Body Weight ◽  
Left Ventricular ◽  
Kidney Cortex ◽  
Sprague Dawley ◽  
Aortic Constriction ◽  
Compensatory Response ◽  
Abdominal Aortic

The characteristics of dopamine receptors were studied in heart and kidney using the radiolabeled receptor assay of [3H]spiperone during the development of cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 3, 14, and 28 days thereafter. Sham-operated animals without aortic constriction were used as control. Although the ratio of left ventricular weight to total body weight was significantly increased 14 and 28 days after aortic constriction in animals, [3H]spiperone binding in left ventricular membrane was increased as early as 3 days after aortic constriction. At 14 days, the binding was still elevated and, by 28 days, it returned to control values. In contrast, membranes obtained from kidney cortex showed an elevation of [3H]spiperone binding only at 28 days after aortic constriction; at 3 days the binding values were decreased. A reciprocal correlation was found between the number of dopamine receptors and the activity of Na(+)-K(+)-ATPase at 28 days of aortic constriction; the enzyme activity, as measured by the release of 32Pi from [gamma-32P]ATP, was decreased in kidney cortex. Autoradiographic data also showed an increased number of dopamine receptors in kidney at 28 days after abdominal aortic constriction. These results suggest that the dopamine receptor is increased very early in heart in response to pressure overload as a result of a compensatory response to maintain an optimal left ventricular output. Kidney dopamine receptors are triggered at a later stage possibly to maintain fluid homeostasis secondary to the cardiac hypertrophic process.

Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension

2004 ◽  
Vol 19 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Beverly L. Falcón ◽  
Jillian M. Stewart ◽  
Erick Bourassa ◽  
Michael J. Katovich ◽  
Glenn Walter ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Gene Transfer ◽  
Cardiac Hypertrophy ◽  
Rat Model ◽  
Lentiviral Vector ◽  
Receptor Gene ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley

The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng·kg−1·min−1 of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure (BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.

scholarly journals Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy

2016 ◽  
Vol 45 (2) ◽  
pp. 344-352 ◽  
Author(s):  
Michael E. Dunn ◽  
Thomas G. Manfredi ◽  
Kevin Agostinucci ◽  
Steven K. Engle ◽  
Josh Powe ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Left Ventricular ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sprague Dawley Rats ◽  
Exercise Induced

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

Abstract 63: Reduction in Glucocorticoid Receptor Expression Attenuates Pressure Overload-induced Cardiac Hypertrophy and Promotes Heart Failure in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Rongxue Wu ◽  
Maura Knapp ◽  
Mei Zheng ◽  
James K Liao
Keyword(s):  
Heart Failure ◽  
Glucocorticoid Receptor ◽  
Cardiac Hypertrophy ◽  
Imaging System ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Heart Weight ◽  
Homozygous Mutation ◽  
Compensatory Mechanism

Background: Left ventricular hypertrophy (LVH) is an independent risk factor for heart failure and sudden death. In addition, LVH is also a compensatory mechanism that helps the heart cope with pressure overload. Stress is considered one factor that is related to cardiac outcomes. Glucocorticoids are primary stress hormones, whose role in the heart is poorly understood. Here, we hypothesize that a reduction in the expression of the glucocorticoid receptor (GR) would decrease cardiac hypertrophy in response to pressure overload. Methods and Results: The GR homozygous mutation (GR-/-) is embryonic lethal. However, GR heterozygous mice (GR+/-) show a normal phenotype. We subjected GR+/- mice to transverse aortic constriction (TAC). At four weeks after TAC, the ratio of heart weight to tibia length increased significantly in wild-type mice (control) littermates compared with GR+/- mice. Cardiac myocyte size was also smaller in GR+/- mice vs controls, suggesting an attenuated cardiac growth response in these mice. In addition, GR+/- hearts displayed increased cell death and enhanced fibrosis in response to TAC. Cardiac function, determined by EF% and FS% (measured using the Vevo2100 imaging system), was significantly reduced in GR+/- mice compared with controls at eight weeks post-operation, while LVEDD was increased. Together, with the increased ratio of lung weight to body weight in GR+/- mice at eight weeks following TAC, this suggests an exaggerated heart failure in GR+/- mice. In vitro, hydrocortisone-induced cell growth in H9c2 cells was abolished by GR knockdown using siRNA. Finally, we looked at the mechanisms by which GR may play a role in the development of hypertrophy. We found reduced ERK-JNK activity in GR+/- hearts, suggesting that the reduced hypertrophic response in GR+/- mice occurs, at least partially, through abolished JNK and ERK activity. Conclusion: The glucocorticoid receptor is required for cardiac hypertrophy and protects the heart from heart failure during cardiac pressure overload.

Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats

1990 ◽  
Vol 259 (2) ◽  
pp. H324-H332 ◽  
Author(s):  
K. M. Baker ◽  
M. I. Chernin ◽  
S. K. Wixson ◽  
J. F. Aceto
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Abdominal Aorta ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Nuclease Mapping

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

2006 ◽  
Vol 290 (4) ◽  
pp. H1635-H1641 ◽  
Author(s):  
Tue E. H. Christoffersen ◽  
Mark Aplin ◽  
Claes C. Strom ◽  
Soren P. Sheikh ◽  
Ole Skott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Natriuretic Peptide Receptor ◽  
Angiotensin System ◽  
Peptide Receptor

Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg·kg−1·day−1) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression. The ascending aorta was banded in 84 rats during Hypnorm/Dormicum-isoflurane anesthesia; after 4 wk the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 wk later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% ( P < 0.001) and 520% ( P < 0.01), respectively, after 8 wk; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of left ventricular weight but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle.

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