Abstract 059: N-acylhydrazone Derivative Improves Cardiac Hypertrophy and Dysfunction in Spontaneously Hypertensive Rats Submitted to Myocardial Infarction

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Gisele Zapata-Sudo ◽  
Jaqueline S Silva ◽  
Sharlene L Pereira ◽  
Rodolfo C Maia ◽  
Carlos A Fraga ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Ventricular Dysfunction ◽  
Volume Fraction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Aims: Ventricular dysfunction is observed in arterial hypertension and myocardial infarction (MI). The N -acylhydrazone derivative, 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), which has been described as a potent cardiac inotropic agent with vasodilator properties, was orally administrated in spontaneously hypertensive rats (SHR) submitted to experimental MI. Methods and Results: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male SHR (12 - 14 week-old) were randomly divided in sham-operated (SHAM) and infarcted groups (MI) and were treated or not with LASSBio-294 (20 mg/kg p.o.) during 8 weeks. Under sevoflurane anesthesia, the animals were submitted to a ligature of the anterior descending coronary artery to produce the MI. After 8 weeks, rats were submitted to treadmill test and also, the following hemodynamic parameters were analyzed: left ventricular end diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and LV contractility (dp/dt max ). Hypertrophy was measured using the relation between heart weight to body weight (heart/BW). The volume fraction of collagen (%) was determined by measuring the area of stained tissue within a given field by picrosirius red staining. The results are presented in the following table. Conclusions: Treatment of infarcted SHR with LASSBio-294 reduced intolerance to exercise, ventricular dysfunction, cardiac hypertrophy and fibrosis.

Abstract 69: Reduction of Diastolic Dysfunction by Treatment of a Combination of Agonists of Adenosine Receptor in Spontaneously Hypertensive Rats Submitted to Myocardial Infarction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Gisele Zapata-Sudo ◽  
Tais N Frazão ◽  
Jaqueline S da Silva ◽  
Eliezer J Barreiro ◽  
Carlos A Fraga ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Mean Blood Pressure ◽  
Heart Weight ◽  
Hemodynamic Parameters ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Introduction: This work investigated the cardioprotective actions of the combination of a positive inotropic agent (LASSBio-294 ) and a potent vasodilator (LASSBio-897) in spontaneously hypertensive rats (SHR) submitted to myocardial infarction (MI). Methods: Twenty four SHR (180-200 g) were randomly divided in sham-operated (SO) and infarcted groups (MI) and each group subdivided in two: treatment with vehicle (DMSO) or with LASSBio-294 + LASSBio-897 (5mg/kg each, p.o.) during 8 weeks. After treatment period, the animals were submitted to echocardiography to determine the anterior wall thickness (AWT), ejection fraction (EF), fractional shortening (FS) and the ratio of early and late transmitral filling velocity (E/A). In addition, the following hemodynamic parameters were evaluated: mean blood pressure (MBP), left ventricular end diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and LV contractility and relaxation (dp/dt max ). Hypertrophy was measured using the relation between heart weight to body weight (HW/BW). The volume fraction of collagen (%) was determined by measuring the area of H&E stained tissue within a given field. Results: MI induced in SHR promoted a decrease in AWT; EF; FS and E/A from 2.0 ± 0.4 to 1.6 ± 0.9 mm; from 53.1 ± 7.5 to 25.3 ± 6.4 %; from 40.0 ± 0.9 to 25.3 ± 11.0 %; and from 1.4 ± 0.1 to 0.9 ± 0.1, respectively. Treatment with the combination of drugs, increased AWT to 2.5 ± 0.6 mm; EF to 73.2 ± 1.0 %; FS to 43.5 ± 6.6%; and E/A to 1.3 ± 0.1. Increase of LVEDP from 4.6 ± 0.3 to 30.0 ± 3.6 mmHg and duplicated oxygen consumption were observed in MI-SHR. The negative dP/dt was reduced from 6152 ± 1015 to 3957 ± 1225 mm Hg/s. After treatment, all hemodynamic parameters were restored to values similar to SO group. Mean blood pressure which was increased after MI from 168. 2 ± 18.6 to 197.7 ± 10.7 returned to 137.0 ± 19.3 mm Hg after treatment. Increased deposition of colagen from 15.1 ± 3.9 to 24.0 ± 0.9 % induced by MI was prevented with treatment with the combination of drugs (12.9 ± 3.8 %). Conclusion: Oral administration of the combination of LASSBio-294 and LASSBio-897 could be considered promising in preventing cardiac dysfunction in SHR submitted to MI.

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.

scholarly journals Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S84-S90 ◽  
Author(s):  
Daniel Casellas ◽  
Abderraouf Herizi ◽  
Annie Artuso ◽  
Albert Mimran ◽  
Bernard Jover
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renal Injury ◽  
Spontaneously Hypertensive Rats ◽  
Candesartan Cilexetil ◽  
Vascular Lesions ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
Renal Protection ◽  
Spontaneously Hypertensive

Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against NG-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5—20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.

scholarly journals Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

2016 ◽  
Vol 39 (1) ◽  
pp. 229-241 ◽  
Author(s):  
Jian Yang ◽  
Yu-Ning Chen ◽  
Zao-Xian Xu ◽  
Yun Mou ◽  
Liang-Rong Zheng
Keyword(s):  
Cardiac Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Heart Weight ◽  
Farnesyl Pyrophosphate ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Aortic Remodeling

Background: In our previous study, farnesyl pyrophosphate synthase (FPPS) was shown to be increased in spontaneously hypertensive rats (SHR) and in mice with angiotensin-II induced cardiac hypertrophy. Overexpression of FPPS induced cardiac hypertrophy and fibrosis in mice, accompanied by an increase in the synthesis of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). In the present study, we investigated the mechanisms of reversing cardiovascular remodeling in SHR by inhibiting FPPS. Methods and Results: Six-week-old rats were given vehicle or an FPPS inhibitor (alendronate, 100 ug/kg/d) daily for twelve weeks by osmotic mini-pump. The results demonstrated that FPPS inhibition attenuated cardiac hypertrophy and fibrosis in SHR as shown by the heart weight to body weight ratio, echocardiographic parameters, and histological examination. In addition, FPPS inhibition attenuated aortic remodeling as shown by reduced media thickness, media cross-sectional area and collagen of the aorta as well as SBP, DBP, MBP. Furthermore, 12 weeks of alendronate treatment significantly decreased FPP and GGPP levels, RhoA activation and geranylgeranylation in the heart and aorta, all of which were significantly upregulated in SHR compared with normotensive Wistar-Kyoto rats. Conclusion: Taken together, these results indicate that chronic treatment with alendronate decreases the development of cardiac and aortic remodeling, by a pathway which involves inhibition of the geranylgeranylation and activation of RhoA.

Haemodynamic and Neurohumoral Changes in Spontaneously Hypertensive Rats with Aortocaval Fistulae

1993 ◽  
Vol 84 (5) ◽  
pp. 531-535 ◽  
Author(s):  
Tamiko Oka ◽  
Hikaru Nishimura ◽  
Masakuni Ueyama ◽  
Jiro Kubota ◽  
Keishiro Kawamura
Keyword(s):  
Heart Failure ◽  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Left Ventricular ◽  
Heart Weight ◽  
Stroke Index ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Output Heart Failure ◽  
High Output

1. Our aim was to evaluate the effects of an aortocaval fistula (1 mm) on cardiorenal haemodynamics, cardiac hypertrophy and neurohumoral factors in spontaneously hypertensive rats and to compare the results with those observed in Wistar rats at 2 weeks after fistulae placement. Sham-operated spontaneously hypertensive rats and Wistar rats served as controls. 2. Heart weight was significantly increased in spontaneously hypertensive rats (34%) and in Wistar rats (43%) at 2 weeks after fistula creation. Left ventricular systolic pressure and dp/dtmax. were significantly decreased (both P <0.01) in spontaneously hypertensive rats with fistulae which had higher left ventricular end-diastolic pressure than Wistar rats with fistulae (P <0.01). Signs of circulatory congestion (ascites, tachypnoea, prostration) were observed only in the overloaded spontaneously hypertensive rats (45%). Cardiac index was comparably increased in both fistulae groups due to an increase in stroke index, since heart rate was not increased. 3. Fistulae placement decreased renal blood flow and kidney weight, and increased blood urea nitrogen to a greater degree in spontaneously hypertensive rats (all P <0.05); serum creatinine levels were unaltered. Plasma noradrenaline concentration was increased in spontaneously hypertensive rats with fistulae (P <0.05), whereas plasma renin activity was not changed. 4. Thus, spontaneously hypertensive rats with fistulae developed overt haemodynamic signs of high-output heart failure with frequent ascites and dyspnoea, whereas most of these findings were milder or absent in Wistar rats. This model provides an opportunity to evaluate the pathophysiological and pharmacological responses in high-output heart failure.

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