Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs

2001 ◽  
Vol 281 (4) ◽  
pp. H1704-H1710 ◽  
Author(s):  
John P. Bell ◽  
Salah I. Mosfer ◽  
Derek Lang ◽  
Francis Donaldson ◽  
Malcolm J. Lewis
Keyword(s):  
Body Weight ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Antioxidant Vitamin ◽  
Ang Ii ◽  
Text Production ◽  
Tnf Α

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O[Formula: see text]) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-α levels, and O[Formula: see text] production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.

Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied rat heart

1994 ◽  
Vol 266 (2) ◽  
pp. H749-H756
Author(s):  
F. Tomita ◽  
A. L. Bassett ◽  
R. J. Myerburg ◽  
S. Kimura
Keyword(s):  
Body Weight ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Body Weight Ratio ◽  
The Right ◽  
Hypertrophied Ventricle ◽  
Concomitant Exposure

Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by beta-adrenergic stimulation are involved, we compared the effects of adenosine 3',5'-cyclic monophosphate (cAMP) on SR Ca2+ uptake between normal and pressure-overloaded hypertrophied hearts using saponin-skinned rat left ventricular muscles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4–6 wk before study. Age-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio 60.8%. The SR was loaded by exposing the muscles to 10(-6) M Ca2+ solution; SR Ca2+ release was induced by 5 or 25 mM caffeine, and the amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. Concomitant exposure to 10(-4) M cAMP did not influence caffeine-induced Ca2+ release in either normal or hypertrophied fibers. When 10(-4) M cAMP was applied during the Ca(2+)-loading periods, the amount of Ca2+ accumulated by the SR increased in both normal and hypertrophied fibers. However, the extent of increase was significantly smaller in hypertrophied fibers than in normal fibers [10.9 +/- 1.7 and 27.4 +/- 5.3% in 1 min of Ca2+ loading (P < 0.05), 12.2 +/- 3.2 and 24.7 +/- 3.8% in 4 min of Ca2+ loading (P < 0.05), respectively]. cAMP (10(-4) M) shifted the force-pCa relationship to the right similarly in normal and hypertrophied muscles, and there was no difference in the force-pCa relationship between the two groups either with or without cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Impacts of a Specific Cyclooxygenase-2 Inhibitor on Pressure Overload–Induced Myocardial Hypertrophy in Rats

2019 ◽  
Vol 22 (6) ◽  
pp. E432-E437
Author(s):  
Zhixiang Xie ◽  
Shuyin Wang ◽  
Zijing Liang ◽  
Liangbo Zeng ◽  
Rongde Lai ◽  
...  
Keyword(s):  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cyclooxygenase 2 ◽  
Inflammatory Factors ◽  
Heart Weight ◽  
Sham Operation ◽  
Surgery Group ◽  
Tnf Α

Objective: The aim of this study was to observe the impacts of the specific cyclooxygenase-2 inhibitor celecoxib on cardiac structures, functions, and inflammatory factors during the process of pressure overload–induced myocardial hypertrophy. Methods: Twenty-four male Sprague Dawley rats were randomly divided into 3 groups: the sham operation group, the surgery group, and the celecoxib group. The model was established according to the abdominal aortic coarctation method. Results: At 16 weeks, rats in the celecoxib group were fed a celecoxib-mixed diet (10 mg/kg) for 8 consecutive weeks. At week 24 after model establishment, the cardiac structures and functions were observed; changes in the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), C-reactive protein (CRP), and uric acid (UA) were detected; and the contents of Smad1/2/3 proteins (Smad1, Smad2, and Smad3)  were determined. Left ventricular mass index, the heart weight/body weight ratio, and TNF-α, TGF-β, PGE2, CRP, and UA levels of the celecoxib group were all significantly decreased relative to those of the surgery group (P < .05); moreover, the cardiac functions were significantly improved compared to those of the surgery group (P < .05). Conclusions: These results show that inflammatory factors are involved in the myocardial hypertrophy process and that celecoxib may reverse myocardial hypertrophy through a variety of pathways.

Abstract 1393: Inhibition of Cardiac Remodeling by Pravastatin is Associated with Amelioration of Endoplasmic Reticulum Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hui Zhao ◽  
Yulin Liao ◽  
Tetsuo Minamino ◽  
Yoshihiro Asano ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
Cardiac Remodeling ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Stress Signaling ◽  
Body Weight Ratio ◽  
Stress Signaling Pathway

Background We previously reported that prolonged endoplasmic reticulum (ER) stress contributes to progression from cardiac hypertrophy to heart failure. Statins have an inhibitory effect on cholesterol synthesis, oxidative stresses, protein synthesis and production of inflammatory cytokines, all of which could be associated with ER stress. However, it is unknown whether statins can ameliorate ER stress in heart disease. This study was designed to investigate whether pravastatin could inhibit cardiac remodeling and ameliorate ER stress caused by pressure overload or tumor necrosis factor α (TNF α ). Methods and Results Cardiac hypertrophy was induced by transverse aortic constriction (TAC) for four weeks in C57BL/6 male mice. Either pravastatin (5 mg/kg/d, n=20, TAC+prava group) or its vehicle (n=20) was orally administered to mice. The ER stress signaling pathway was also studied in pressure-overloaded mice hearts and in cultured cardiomyocytes treated with TNF α (10ng/ml) for 24 hours. Four weeks after TAC, both heart-to-body weight ratio (8.68 ± 1.23 in TAC group, 6.92 ± 1.11 in TAC+prava group) and lung-to-body weight ratio (11.08 ± 2.58 in TAC group, 7.92± 3.56 in TAC+prava group) became significantly lower in pravastatin-treated mice than in the TAC group. Left ventricular fractional shortening and left ventricular ejection fraction (LVFS and LVEF) were larger in TAC+prava group (48.0±1.9 % and 80±1.9% respectively) compared with TAC group (LVFS and LVEF, 34.8 ±1.4% and 65 ±3%; P<0.01 VS TAC group each). Markers of ER stress such as an increase in ER chaperones and CHOP expressions and enhanced phosphorylation of eIF2 α were observed in the hearts of TAC mice, while pravastatin treatment significantly blunted these changes. Pravastatin-treated TAC mice also showed a decrease of cardiac apoptosis. Cardiac expression of TNF α was increased in TAC mice, and TNF α induced ER stress in cultured neonatal rat cardiomyocytes, either of which was significantly inhibited by pravastatin. Conclusions These findings indicate that pravastatin inhibits cardiac remodeling in mice subjected to pressure overload, and this action is associated with inhibition of the ER stress signaling pathway.

Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats

2007 ◽  
Vol 293 (6) ◽  
pp. E1606-E1614 ◽  
Author(s):  
Md. Shenuarin Bhuiyan ◽  
Norifumi Shioda ◽  
Kohji Fukunaga
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Body Weight Ratio

To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic-banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. Effects on LV morphology and function were assessed using echocardiography, and expression of protein levels was determined by Western blot analysis. The heart-to-body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared with the OVX group and in the PO group compared with sham. The LV weight-to-body weight ratio was also significantly increased in the OVX-PO group compared with the OVX group and in the PO group compared with sham. The most significant increases in LV end diastolic pressure, LV developed pressure, and ±dp/d tmax were observed in the OVX-PO group compared with the OVX group and represent compensatory phenotypes against hypertrophy. Both endothelial nitric oxide (eNOS) synthase expression and activity was markedly reduced in the OVX-PO group, and protein kinase B (Akt) activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significantly increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subjected to ovariectomy are unable to compensate for hypertrophy, showed deteriorated heart function, and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.

Angiotensin II in cardiac pressure-overload hypertrophy in fetal sheep

2001 ◽  
Vol 281 (6) ◽  
pp. R2037-R2047 ◽  
Author(s):  
Jeffrey L. Segar ◽  
Gregory B. Dalshaug ◽  
Kurt A. Bedell ◽  
Oliva M. Smith ◽  
Thomas D. Scholz
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Mrna Levels ◽  
Ang Ii ◽  
Body Weight Ratio ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Selective Increase

We previously demonstrated in fetal sheep that blockade of ANG II type 1 (AT1) receptors did not attenuate an increase in right ventricle (RV) mass resulting from partial occlusion of the pulmonary artery (PA). We have now determined the effects of AT2-receptor blockade (PD-123319, 10 mg · kg−1· day−1continuous iv) on the response of the fetal RV to PA banding for 7 days. Four groups of fetuses (each n = 7) were studied beginning at 126 ± 1 days gestation (term 145 days). RV weight-to-body weight ratio (RV wt/body wt) increased ( P < 0.05) in PA-banded (6.00 ± 0.09 g/kg) and PA-banded + PD-123319 (6.19 ± 0.27 g/kg) compared with control (5.17 ± 0.17 g/kg) and PD-123319-infused (5.27 ± 0.35 g/kg) fetuses (means ± SE). Blood pressure and heart rate were similar in all groups. PD-123319 produced a decrease ( P < 0.05) in AT1but not AT2mRNA levels in both fetal ventricles. To examine the effect of ANG II on fetal heart growth, twin fetal sheep were infused with either ANG II (twin received vehicle) or phenylephrine (Phe) (twin received vehicle) continuously for 7 days. Mean arterial blood pressure was 20–25 mmHg higher in ANG II and Phe fetuses compared with controls. The rate-pressure product was similar in ANG II and Phe fetuses and 40–50% greater than controls. Phe resulted in no change in RV wt/body wt or left ventricle-to-body weight ratio (LV wt/body wt) compared with controls. In contrast, ANG II produced a selective increase (27 ± 5%, P < 0.05) in LV wt/body wt; no effect was seen on the RV. ANG II produced a decrease ( P < 0.05) in LV but not RV AT1mRNA levels compared with controls; no effect was seen with Phe. The data demonstrate that in the ovine fetus, AT2receptors do not contribute to the maintenance of blood pressure or the development of pressure-overload RV hypertrophy. Elevated ANG II levels produce a selective increase in LV mass in the fetal sheep that is, in part, independent of increased systolic load.

Downregulation of cyclin-dependent kinase inhibitors p21 and p27 in pressure-overload hypertrophy

1997 ◽  
Vol 273 (3) ◽  
pp. H1358-H1367 ◽  
Author(s):  
J. M. Li ◽  
G. Brooks
Keyword(s):  
Body Weight ◽  
Kinase Inhibitors ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Growth Potential ◽  
Cyclin Dependent Kinase ◽  
Body Weight Ratio ◽  
Adaptive Growth ◽  
Adult Rat

We postulated that the cyclin-dependent kinase inhibitors p21 and p27 could regulate the alterations in growth potential of cardiomyocytes during left ventricular hypertrophy (LVH). LVH was induced in adult rat hearts by aortic constriction (AC) and was monitored at days 0, 1, 3, 7, 14, 21, and 42 postoperation. Relative to sham-operated controls (SH), left ventricle (LV) weight-to-body weight ratio in AC increased progressively with time without significant differences in body weight or right ventricle weight-to-body weight ratio. Atrial natriuretic factor mRNA increased significantly in AC to 287% at day 42 compared with SH (P < 0.05), whereas p21 and p27 mRNA expression in AC rats decreased significantly by 58% (P < 0.03) and 40% (P < 0.05) at day 7, respectively. p21 and p27 protein expression decreased significantly from days 3 to 21 in AC versus SH, concomitant with LV adaptive growth. Immunocytochemistry showed p21 and p27 expression in cardiomyocyte nuclei. Thus downregulation of p21 and p27 may modulate the adaptive growth of cardiomyocytes during pressure overload-induced LVH.

Abstract P210: Central Blockade Of Tumor Necrosis Factor-Á-Converting Enzyme (tace) Ameliorates Neuroinflammation, Sympathetic Excitation And Cardiac Dysfunction In Heart Failure Rat

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yang Yu ◽  
Baojian Xue ◽  
Hanzeng Li ◽  
Qing Chen ◽  
Mingxuan Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Cardiac Dysfunction ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Male Rats ◽  
Tnf Α ◽  
Necrosis Factor

TACE is a key metalloprotease involved in ectodomain shedding of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-α. We previously reported that TACE-mediated production of TNF-α in the hypothalamic paraventricular nucleus (PVN) contributes to the sympathetic excitation in heart failure (HF). Additionally, the upregulated TGF-α in the PVN transactivates the epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK) 1/2 in HF. Here we sought to determine whether central inhibition of TACE attenuates neuroinflammation and prevents the progress of HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). These rats were treated with bilateral PVN microinjection of a TACE siRNA or control siRNA while some rats received a 4-week intracerebroventricular (ICV) infusion of TACE inhibitor TAPI-0 or vehicle. Compared with Sham rats, HF rats treated with control siRNA, had higher (*P<0.05) levels of TNF-α (7.88±1.32* vs 2.77±0.98 pg/mL) and TGF-α (28.27±2.76* vs 11.62±2.48 pg/mL) in cerebrospinal fluid, and increased mRNA expression of TACE (2.53±0.30* vs 1.04±0.12), TNF-α (3.43±0.55* vs 1.03±0.11), TNF-α receptor 1 (2.32±0.27* vs 1.07±0.19), cyclooxygenase-2 (2.96±0.31* vs 1.10±0.19) and TGF-α (2.68±0.41* vs 1.06±0.14) in the PVN, but these levels were markedly reduced (39-54%*) in TACE siRNA-treated HF rats. Compared with control HF rats, HF rats treated with TACE siRNA had reduced expression of phosphorylated (p-) NF-κB p65 (1.27±0.14 vs 0.84±0.07*), p-EGFR (0.52±0.05 vs 0.37±0.04*) and p-ERK1/2 (1.06±0.10 vs 0.62±0.09*) in the PVN. Moreover, the elevated plasma norepinephrine levels, lung/body weight, heart/body weight and left ventricular (LV) end-diastolic pressure along with decreased LV dP/dt max in HF rats-treated with control siRNA were significantly attenuated in HF rats treated with TACE siRNA. Treatments with TACE siRNA in the PVN also improved the indicators of cardiac hypertrophy and fibrosis of HF. ICV infusion of TAPI-0 had the similar effects with PVN TACE siRNA on these variables in HF. These data indicate that central interventions suppressing TACE activity ameliorate neuroinflammation, sympathetic activation and cardiac dysfunction in HF.

Cardiac vasculature and flow during pressure-overload hypertrophy

1986 ◽  
Vol 251 (5) ◽  
pp. H1031-H1037 ◽  
Author(s):  
E. A. Breisch ◽  
F. C. White ◽  
L. E. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional ◽  
Ventricle Hypertrophy ◽  
Aortic Cuff

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

Abstract 297: Cardiac Transforming-growth-factor β-stimulated Clone 22 Gene Expression By Hypertrophic Stimuli

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Annina Kelloniemi ◽  
Jani Aro ◽  
Elina Koivisto ◽  
Heikki Ruskoaho ◽  
Jaana Rysä
Keyword(s):  
Growth Factor ◽  
Gene Transfer ◽  
Transforming Growth Factor ◽  
Pressure Overload ◽  
Transforming Growth Factor Β ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Ang Ii ◽  
Sd Rats

Objectives: Transforming-growth-factor β-stimulated clone 22 (TSC-22) is a leucine zipper protein expressed in many tissues and possessing various transcription-modulating activities. However, its function in the heart remains largely unknown. The aim of the present study was to characterize the cardiac TSC-22 expression. Methods: Acute pressure overload was accomplished in conscious Sprague-Dawley (SD) rats by intravenous infusion of arginine 8 -vasopressin (AVP, 0.05 μg/kg/min) for 4 hours and subcutaneous infusion of angiotensin II (Ang II, 33 μg/kg/h) with and without Ang II receptor type 1 blocker losartan (400 μg/kg/h) by using osmotic minipumps for 2 weeks. Adenovirus-mediated intramyocardial gene transfer of TSC-22 was performed into left ventricle (LV) of SD rats. Experimental myocardial infarction (MI) was produced by ligation of the left anterior descending coronary artery. Cultured neonatal rat ventricular myocytes (NRVM) were treated with endothelin-1 (ET-1, 100 nM). Results: A significant 1.6-fold increase ( P <0.05) in LV TSC-22 mRNA levels was noted already after 1 hour AVP infusion. Moreover, Ang II infusion markedly upregulated TSC-22 expression, LV mRNA levels being highest at 6 hours (11-fold, P <0.001). Simultaneous infusion of losartan completely abolished Ang II-induced increase in TSC-22 mRNA levels. Adenovirus-mediated gene transfer of TSC-22 into LV resulted a 1.9-fold ( P <0.001) increase in TSC-22 mRNA levels, accompanied by upregulated BNP mRNA levels (1.4-fold, P <0.01). In response to experimental MI, TSC-22 mRNA levels were elevated 4.1-fold ( P <0.001) at 1 day and 1.9-fold ( P <0.05) at 4 weeks. In cultured NRVM, ET-1 treatment increased TSC-22 mRNA levels from 1 h to 24 h, the greatest increase being observed at 12 h (2.7-fold, P <0.001). TSC-22 protein levels were upregulated from 4 h to 24 h with the highest increase at 24 h (4.7-fold, P <0.01). Conclusion: These results indicate that TSC-22 expression is rapidly activated in response to pressure overload, MI and in ET-1 treated cultured NRVM. Moreover, adenovirus-mediated overexpression of TSC-22 mRNA was associated with elevated left ventricular BNP mRNA levels.

Sign in / Sign up

Export Citation Format

Share Document