Protective Effects of Galium verum L. Extract against Cardiac Ischemia/Reperfusion Injury in Spontaneously Hypertensive Rats

Galium verum L. (G. verum, lady’s bedstraw) is a perennial herbaceous plant, belonging to the Rubiaceae family. It has been widely used throughout history due to multiple therapeutic properties. However, the effects of this plant species on functional recovery of the heart after ischemia have still not been fully clarified. Therefore, the aim of our study was to examine the effects of methanol extract of G. verum on myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats (SHR), with a special emphasis on the role of oxidative stress. Rats involved in the research were divided randomly into two groups: control (spontaneously hypertensive rats (SHR)) and G. verum group, including SHR rats treated with the G. verum extract (500 mg/kg body weight per os) for 4 weeks. At the end of the treatment, in vivo cardiac function was assessed by echocardiography. Rats were sacrificed and blood samples were taken for spectrophotometric determination of systemic redox state. Hearts from all rats were isolated and retrogradely perfused according to the Langendorff technique. After a stabilization period, hearts were subjected to 20-minute ischemia, followed by 30-minute reperfusion. Levels of prooxidants were spectrophotometrically measured in coronary venous effluent, while antioxidant enzymes activity was assessed in heart tissue. Cell morphology was evaluated by hematoxylin and eosin (HE) staining. 4-week treatment with G. verum extract alleviated left ventricular hypertrophy and considerably improved in vivo cardiac function. Furthermore, G. verum extract preserved cardiac contractility, systolic function, and coronary vasodilatory response after ischemia. Moreover, it alleviated I/R-induced structural damage of the heart. Additionally, G. verum extract led to a drop in the generation of most of the measured prooxidants, thus mitigating cardiac oxidative damage. Promising potential of G. verum in the present study may be a basis for further researches which would fully clarify the mechanisms through which this plant species triggers cardioprotection.

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

Clinical Science ◽

10.1042/cs20030268 ◽

2004 ◽

Vol 106 (3) ◽

pp. 337-343 ◽

Cited By ~ 15

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y07-073 ◽

2007 ◽

Vol 85 (8) ◽

pp. 783-789 ◽

Cited By ~ 19

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.

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Mitochondrial genome modulates myocardial Akt/Glut/HK salvage pathway in spontaneously hypertensive rats adapted to chronic hypoxia

Physiological Genomics ◽

10.1152/physiolgenomics.00040.2017 ◽

2018 ◽

Vol 50 (7) ◽

pp. 532-541 ◽

Cited By ~ 1

Author(s):

Iveta Nedvedova ◽

David Kolar ◽

Barbara Elsnicova ◽

Daniela Hornikova ◽

Jiri Novotny ◽

...

Keyword(s):

Mitochondrial Genome ◽

Spontaneously Hypertensive Rats ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Male Rats ◽

Brown Norway ◽

Adaptation To Hypoxia ◽

Left Ventricular Myocardium ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

Recently we have shown that adaptation to continuous normobaric hypoxia (CNH) decreases myocardial ischemia/reperfusion injury in spontaneously hypertensive rats (SHR) and in a conplastic strain (SHR-mtBN). The protective effect was stronger in the latter group characterized by a selective replacement of the SHR mitochondrial genome with that of a more ischemia-resistant Brown Norway strain. The aim of the present study was to examine the possible involvement of the hypoxia inducible factor (HIF)-dependent pathway of the protein kinase B/glucose transporters/hexokinase (Akt/GLUT/HK) in this mitochondrial genome-related difference of the cardioprotective phenotype. Adult male rats were exposed for 3 wk to CNH ([Formula: see text] 0.1). The expression of dominant isoforms of Akt, GLUT, and HK in left ventricular myocardium was determined by real-time RT-PCR and Western blotting. Subcellular localization of GLUTs was assessed by quantitative immunofluorescence. Whereas adaptation to hypoxia markedly upregulated protein expression of HK2, GLUT1, and GLUT4 in both rat strains, Akt2 protein level was significantly increased in SHR-mtBN only. Interestingly, a higher content of HK2 was revealed in the sarcoplasmic reticulum-enriched fraction in SHR-mtBN after CNH. The increased activity of HK determined in the mitochondrial fraction after CNH in both strains suggested an increase of HK association with mitochondria. Interestingly, HIF1a mRNA increased and HIF2a mRNA decreased after CNH, the former effect being more pronounced in SHR-mtBN than in SHR. Pleiotropic effects of upregulated Akt2 along with HK translocation to mitochondria and mitochondria-associated membranes can potentially contribute to a stronger CNH-afforded cardioprotection in SHR-mtBN compared with progenitor SHR.

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Soyabean protein hydrolysate prevents the development of hypertension in spontaneously hypertensive rats

British Journal Of Nutrition ◽

10.1079/bjn20041218 ◽

2004 ◽

Vol 92 (3) ◽

pp. 507-512 ◽

Cited By ~ 44

Author(s):

Hsin-Yi Yang ◽

Suh-Ching Yang ◽

Jiun-Rong Chen ◽

Ya-Hui Tzeng ◽

Bor-Cheng Han

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Plasma Lipids ◽

Protein Hydrolysate ◽

Ace Inhibition ◽

Inhibitory Effect ◽

Left Ventricular ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

The aim of the present study was to investigate the anti-hypertensive and angiotensin-converting enzyme (ACE) inhibition effects of soyabean protein hydrolysate in spontaneously hypertensive rats (SHR). Soyabean protein hydrolysate was prepared by peptic hydrolysis and was added into the feed of SHR (0 % for the S0 group, 0·5 % for the S1 group, and 1 % for the S2 group) for 12 weeks. Systolic blood pressure and mean blood pressure of the S1 (164·3 (sem 4·7); 128·0 (sem 5·0) mmHg) and S2 (156·8 (sem 1·6); 120·8 (sem 3·4) mmHg) groups were significantly lower than those of the S0 group (199·4 (sem 5·2); 158·3 (sem 7·0) mmHg) at the end of the study. In the analysis of ACE activity, plasma and heart ACE activities of the S1 and S2 groups were significantly lower than those of the S0 group, and there were no significant differences in aorta, kidney, and lung ACE activities among all SHR. Soyabean protein hydrolysate had no significant effect on plasma lipids, electrolytes, or on left ventricular wall or aorta wall thickness. The results suggest that the long-term administration of soyabean protein hydrolysate might retard the development of hypertension in SHR by its inhibitory effect on ACE in vivo.

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Effects of regression of left ventricular hypertrophy following atenolol or bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats.

Japanese Circulation Journal ◽

10.1253/jcj.55.1233 ◽

1991 ◽

Vol 55 (12) ◽

pp. 1233-1245 ◽

Cited By ~ 7

Author(s):

HIDEICHI TANAKA ◽

HIROMI OBATA ◽

TAKASHI HANEDA

Keyword(s):

Left Ventricular Hypertrophy ◽

Cardiac Function ◽

Spontaneously Hypertensive Rats ◽

Ventricular Hypertrophy ◽

Myocardial Metabolism ◽

Left Ventricular ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

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Tolerance to acute ischemia in adult male and female spontaneously hypertensive rats

Physiological Research ◽

10.33549/physiolres.930998 ◽

2007 ◽

pp. 267-274 ◽

Cited By ~ 5

Author(s):

J Bešík ◽

O Szarszoi ◽

J Kuneš ◽

I Netuka ◽

J Malý ◽

...

Keyword(s):

Blood Pressure ◽

Reperfusion Injury ◽

Spontaneously Hypertensive Rats ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Developed Pressure

Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women.

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