Myocardial stretch induced by increased left ventricular diastolic pressure preconditions isolated perfused hearts of normotensive and spontaneously hypertensive rats

1997 ◽  
Vol 92 (6) ◽  
pp. 410-416
Author(s):  
C. Nakagawa ◽  
J. Asayama ◽  
M. Katamura ◽  
S. Matoba ◽  
N. Keira ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Myocardial Stretch ◽  
Perfused Hearts

Abstract 363: Recovery of Exercise Intolerance and Ventricular Dysfunction of Infarcted Spontaneously Hypertensive Rats After Oral Treatment With an Agonist of Adenosine Receptor

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jaqueline S da Silva ◽  
Roberto T Sudo ◽  
Roberto Debom ◽  
Eliezer J Barreiro ◽  
Carlos A Fraga ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Ventricular Dysfunction ◽  
Diastolic Pressure ◽  
Oral Treatment ◽  
Treated Group ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Positive Staining ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Severe ventricular dysfunction is observed in spontaneously hypertensive rats (SHR) submitted to myocardial infarction (MI). The present work evaluates the cardioprotective effects of oral administration of a novel agonist of adenosine A2A receptor, LASSBio-294, in infarcted SHR. Methods: Male SHR (12-14 wks old) were randomly divided into groups: sham and infarcted (MI) which were either treated orally with vehicle or LASSBio-294 (10 mg/kg) for 28 days. Before and after the animals were treated with LASSBio-294, cardiac function and exercise capacity were evaluated through the echocardiography and treadmill test. Mean blood pressure (MBP), left ventricular end diastolic pressure (LVEDP) and negative dP/dt were also determined. Fibrosis in heart sections were detected using H&E staining. Immunohistochemical staining for TNF-alpha and SERCA2a in LV tissues were observed. Results: MI in SHR reduced the running distance from 257.9 ± 13.2 to 39.0 ± 4.4 m which normalized to 296.0 ± 26.4 m after treatment with LASSBio-294. Reduced anterior wall thickness was observed after MI (0.51 ± 0.14 mm) which was prevented with treatment (1.65 ± 0.21 mm). Ratio of early and late transmitral filling velocity was reduced from 1.48 ± 0.09 to 0.99 ± 0.04 and recovered to 1.35 ± 0.07 after treatment. MBP was reduced from 169.0 ± 5.6 to 120.4 ± 7.4 mmHg in SHR-IM treated with LASSBio-294. Increased LVEDP of 25.6 ± 3.2 observed in SHR-IM was reduced to 7.3 ± 1.0 mmHg after treatment. The -dP/dt was reduced in SHR-MI to -5698 ± 408.1 mmHg/s and returned to -7894 ± 631.6 mmHg/s after LASSBio-294 treatment. There was an increase in collagen deposition after MI (from 14.5 ± 3.5 to 59.8 ± 5.4 %) which was prevented with LASSBio-294 treatment (29.5 ± 2.2 %). Increase of positive staining for TNF-α was observed in SHR-MI (from 9.5 ± 1.0 to 32.3 ± 2.1%) which recovered in SHR-MI treated group (14.4 ± 1.3%). Also, the expression of SERCA2a was reduced in ventricular muscle from SHR-IM (from 68.7 ± 5.1 to 21.4 ± 2.3 %) which partially recovered to 40.6 ± 1.19% with LASSBio-294 treatment. Conclusion: LASSBio-294 reduced exercise intolerance, prevented cardiac remodeling and diastolic dysfunction in infarcted SHR.

Abstract 408: Thioredoxin-1 Gene Delivery Induces Hemeoxygenase-1 Mediated Myocardial Preservation after Chronic Infarction in Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
SureshVarma Penumathsa ◽  
Srikanth Koneru ◽  
Mahesh Thirunavukkarasu ◽  
Lijun Zhan ◽  
Nilanjana Maulik
Keyword(s):  
Left Ventricle ◽  
Western Blot ◽  
Infarct Size ◽  
Blot Analysis ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Thioredoxin 1 ◽  
Lac Z

Hypertension the major risk factor for many cardiovascular diseases is a result of multiple causes along with excessive generation of reactive oxygen species resulting in imbalance of redox status. Thioredoxin-1 (Trx-1) is a redox regulatory multifunctional protein with anti-inflammatory, anti-apoptotic and antioxidant effects. In the present study we investigated the therapeutic potential of Adeno-Trx-1 in spontaneously hypertensive rats (SHR). The rats were assigned to four different groups (n = 24) such as (1) normotensive Wistar Kyoto (WKY) (2) SHR (3) SHR +Adeno-Lac-Z (SHRLac-Z) and (4) SHR +Adeno-Trx-1 (SHRTrx-1). Echo-guided gene delivery to the anterior wall of left ventricle was performed using 1x109 pfu of adenovirus constructed with Trx-1 and Lac-Z. Two days after injection of adeno virus, the hearts were subjected to permanent left anterior descending coronary artery occlusion (MI). Left ventricular functions by Echocardiography were examined after 30 days of MI as the significant changes in left ventricle were observed after 4 weeks of MI. Decreased left ventricular inner diameter (7 vs 9 mm) and increased ejection fraction (52 vs 42 %), fractional shortening (28 vs 22 %) was observed in SHRTrx-1 compared to SHR. Infarct size, cardiomyocyte apoptosis and protein expression profiles (by Confocal and Western blot analysis) were observed at predetermined time points i.e after 24 and 48 hours of MI respectively. Decreased infarct size (52% vs 67%), cardiomyocyte apoptosis by TUNEL assay (161 vs 240) and increased expression of Trx-1 and HO-1 were observed in SHRTrx-1 compared to SHR. Confocal results were also confirmed by Western blot analysis. Results documented increased expression of Trx-1 (1.8 fold) and HO-1 (1.4 fold) in SHRTrx-1 as compared to SHR. In addition, we have also observed increased expression of anti-apoptotic protein Bcl-2 (1.7 fold) in SHRTrx-1 treated group compared SHR. Thus our results demonstrate for the first time that the cardioprotective effect of Adeno-Trx-1 therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent a novel mechanism for therapy against hypertension induced post infarction heart failure.

Enalapril attenuates cardiorenal damage in nitric-oxide-deficient spontaneously hypertensive rats

2004 ◽  
Vol 106 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Leila M. M. PEREIRA ◽  
Daniele G. BEZERRA ◽  
Denise L. MACHADO ◽  
Carlos A. MANDARIM-DE-LACERDA
Keyword(s):  
Nitric Oxide ◽  
Body Mass ◽  
Structural Damage ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Genetic Hypertension ◽  
Lv Mass ◽  
Significant Difference

Stereological structural alterations of the heart and kidney were studied in four groups (n=5) of spontaneously hypertensive rats (SHRs) treated for 30 days: (i) control, (ii) NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthesis inhibitor] alone, (iii) enalapril alone and (iv) L-NAME plus enalapril. Blood pressure (BP) was elevated significantly in NO-deficient SHRs (rats receiving L-NAME) or significantly lower in enalapril-treated SHRs. Co-administration of L-NAME and enalapril caused a 20% decrease in BP compared with untreated SHRs. NO-deficient SHRs had a decrease in body mass, but this loss of body mass was prevented efficiently in the enalapril-treated group. Enalapril treatment decreased the left ventricular (LV) mass index in SHRs, even in animals with NO synthesis blocked. NO deficiency in SHRs caused a larger decrease in the number of LV cardiomyocyte nuclei, which had a negative correlation with both LV mass index and BP. The volume-weighted glomerular volume (VWGV) separated the SHRs into two groupings: (i) control and NO-deficient SHRs, and (ii) enalapril- and L-NAME plus enalapril-treated SHRs. There was a significant difference between these two groupings, with VWGV being more than 15% smaller in the latter compared with the former grouping. The present findings reinforce the evidence that enalapril efficiently treats genetic hypertension, and demonstrate that this effect is observed even when NO synthesis is inhibited. Enalapril administration also decreases cardiac and renal structural damage caused by genetic hypertension, as well as by the interaction between genetic hypertension and NO deficiency.

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