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 ◽  
...  

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.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Gisele Zapata-Sudo ◽  
Jaqueline S Silva ◽  
Sharlene L Pereira ◽  
Rodolfo C Maia ◽  
Carlos A Fraga ◽  
...  

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.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nithya Mariappan ◽  
Carrie Elks ◽  
Masudul Haque ◽  
Philip J Ebnezer ◽  
Elizabeth McIIwain ◽  
...  

The transcriptional factor, nuclear factor kappa B (NFkB) plays an important role in the regulation of cytokines. Among the cytokines, tumor necrosis factor-alpha (TNF) plays an important role in cardiovascular pathophysiology. This study was done to determine whether TNF-α blockade with etanercept (ETN) or NFkB blockade with dithiol pyrolidine thiocarbamate (PDTC) attenuate oxidative stress in the paraventricular nucleus (PVN) and contribute to neurohumoral excitation in spontaneously hypertensive rats. Method: Male 20 week old SHR rats were treated with ETN (1 mg/kg BW, sc) or PDTC (100mg/kg BW, ip) for 5 week period. Left ventricular function was measured at baseline (20 weeks) and at 25 weeks using echocardiography. Blood pressure was measured at weekly intervals throughout the study. At the end of the protocol rats were sacrificed the PVN was microdissected for the measurement of cytokines, oxidative stress markers using real time PCR (fold increase compared to WKY controls) and by immunohistochemistry. Superoxide, total reactive oxygen species and peroxynitrite were measured in the PVN and LV using electron paramagnetic resonance. Plasma norepinephrine and epinephrine an indicator of neurohumoral excitation was measured using HPLC-EC. Results: PVN data are tabulated. SHR animals had increased expression of protein and mRNA for cytokines and oxidative stress markers in the PVN and LV with increased MAP and cardiac hypertrophy when compared to WKY rats. Treatment with ETN and PDTC attenuated these increases with PDTC showing marked effect than ETN on hypertrophy and blood pressure responses. Conclusion: These findings suggest that cytokine activation in the PVN contributes to increased oxidative stress and neurohumoral excitation in hypertension.


1985 ◽  
Vol 248 (1) ◽  
pp. H8-H14
Author(s):  
R. P. Crisman ◽  
R. J. Tomanek

We tested the hypothesis that exercise training provides a stimulus that could modify the decrement in mitochondria-to-myofibril volume ratio characteristic of myocardial cells hypertrophied in response to a pressure overload. Spontaneously hypertensive rats (SHR) were trained 5 days/wk on a treadmill at 70-90% maximal VO2 between the ages of 6 and 16 wk corresponding to the development of hypertension and cardiac hypertrophy. The training program increased maximal VO2 and effected a resting bradycardia but did not alter blood pressure, left ventricular hypertrophy, or peak cardiac output. Our stereological data from electron micrographs shows that the decrement in mitochondrial volume density and the increase in myofibril volume density characteristic of SHR compared with their normotensive controls (WKY, Wistar-Kyoto rats) were reversed. Thus the relative volumes of mitochondria and myofibrils and their ratio in trained SHR were similar to those of the WKY group. The similarity was noted in myocytes from both the subepicardium and subendocardium. These data suggest that exercise training facilitates a proportional growth of energy-producing and energy-consuming organelles in SHR and that this effect is not secondary to modification of blood pressure or left ventricular mass.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3758 ◽  
Author(s):  
Paola Marcolongo ◽  
Alessandra Gamberucci ◽  
Gabriella Tamasi ◽  
Alessio Pardini ◽  
Claudia Bonechi ◽  
...  

Blood pressure control in hypertensive subjects calls for changes in lifestyle, especially diet. Tomato is widely consumed and rich in healthy components (i.e., carotenoids, vitamins and polyphenols). The aim of this study was to evaluate the chemical composition and antihypertensive effects of locular gel reconstituted in serum of green tomatoes of “Camone” variety. Tomato serum and locular gel were chemically characterised. The antihypertensive effects of the locular gel in serum, pure tomatine, and captopril, administered by oral gavage, were investigated for 4 weeks in male spontaneously hypertensive and normotensive rats. Systolic blood pressure and heart rate were monitored using the tail cuff method. Body and heart weight, serum glucose, triglycerides and inflammatory cytokines, aorta thickness and liver metabolising activity were also assessed. Locular gel and serum showed good tomatine and polyphenols content. Significant reductions in blood pressure and heart rate, as well as in inflammatory blood cytokines and aorta thickness, were observed in spontaneously hypertensive rats treated both with locular gel in serum and captopril. No significant effects were observed in normotensive rats. Green tomatoes locular gel and serum, usually discarded during tomato industrial processing, are rich in bioactive compounds (i.e., chlorogenic acid, caffeic acid and rutin, as well as the glycoalkaloids, α-tomatine and dehydrotomatine) that can lower in vivo blood pressure towards healthier values, as observed in spontaneously hypertensive rats.


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