Reduction of asymmetric dimethylarginine involved in the cardioprotective effect of losartan in spontaneously hypertensive rats

2007 ◽  
Vol 85 (8) ◽  
pp. 783-789 ◽  
Author(s):  
Dai Li ◽  
Ke Xia ◽  
Nian-Sheng Li ◽  
Dan Luo ◽  
Shan Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Creatine Kinase ◽  
Cardiac Function ◽  
Spontaneously Hypertensive Rats ◽  
Myocardial Injury ◽  
Asymmetric Dimethylarginine ◽  
Left Ventricular ◽  
Ischemia And Reperfusion ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Previous studies have indicated that nitric oxide synthase (NOS) inhibitors can induce an increase of blood pressure and exacerbate myocardial injury induced by ischemia and reperfusion, whereas angiotensin II receptor antagonists protect the myocardium against injury induced by ischemia and reperfusion. Isolated hearts from male spontaneously hypertensive rats (SHR) or male Wistar-Kyoto rats (WKY) were subjected to 20 min global ischemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure, and its first derivatives (±dP/dtmax) were recorded, and serum concentrations of asymmetric dimethylarginine (ADMA) and NO and the release of creatine kinase in coronary effluent were measured. The level of ADMA was significantly increased and the concentration of NO was decreased in SHR. Ischemia and reperfusion significantly inhibited the recovery of cardiac function and increased the release of creatine kinase, and ischemia and reperfusion-induced myocardial injury in SHR was aggravated compared with WKY. Vasodilation responses to acetylcholine of aortic rings were decreased in SHR. Treatment with losartan (30 mg/kg) for 14 days significantly lowered blood pressure, elevated the plasma level of NO, and decreased the plasma concentration of ADMA in SHR. Treatment with losartan significantly improved endothelium-dependent relaxation and cardiac function during ischemia and reperfusion in SHR. Exogenous ADMA also aggravated myocardial injury induced by ischemia and reperfusion in isolated perfused heart of WKY, as shown by increasing creatine kinase release and decreasing cardiac function. The present results suggest that the protective effect of losartan on myocardial injury induced by ischemia and reperfusion is related to the reduction of ADMA levels.

Abstract 1378: NFkb Blockade Attenuate Cytokines And Oxidative Stress In The Paraventricular Nucleus And Decreases Neurohumoral Excitation In Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nithya Mariappan ◽  
Carrie Elks ◽  
Masudul Haque ◽  
Philip J Ebnezer ◽  
Elizabeth McIIwain ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Oxidative Stress Markers ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Stress Markers ◽  
And Oxidative Stress

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.

Exercise training modifies myocardial mitochondria and myofibril growth in spontaneously hypertensive rats

1985 ◽  
Vol 248 (1) ◽  
pp. H8-H14
Author(s):  
R. P. Crisman ◽  
R. J. Tomanek
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Spontaneously Hypertensive Rats ◽  
Pressure Overload ◽  
Volume Ratio ◽  
Volume Density ◽  
Left Ventricular ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

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.

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.

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