Exposure to a "safe" dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats.

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and "safe" dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40 mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50 µg/kg b.w/day) by oral administration along with appropriate controls for 30 days period. The results illustrate that a 'safe' dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly (p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during 'safe' dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

Role of flavonoid troxerutin on blood pressure, oxidative stress and regulation of lipid metabolism.

The objective of the present study was to investigate the effects of troxerutin (TX) on Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. L-NAME (40mg/kg body weight (bw)) administration caused a sustained increase in systolic blood pressure (SBP), levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), tissue lipids (liver and kidney) such as total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), and significant decrease in the activities of enzymatic antioxidants, phospholipids (PL) and levels of non enzymatic antioxidants such as reduced glutathione (GSH), vitamin C and vitamin E. To assess the toxicity if any of TX treatment, hepatic and renal function markers were measured. TX supplementation throughout the experimental period significantly brings back all the above parameters. Among the three doses (25, 50, and 100 mg/kg) of TX, 100 mg/kg dosage exerts optimum protection against L-Name induced hypertension. These results suggest that TX has enough potential to attenuate hypertension, oxidative stress and dyslipidemia in L-NAME induced hypertensive rats.

Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid--Role of HMG-CoA reductase.

The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, kidney fibrosis and lipid alterations in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40 mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and kidney), lipid peroxidation products in tissues (liver and kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l-NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l-NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l-NAME rats. Sinapic acid treatment significantly decreased the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in plasma and liver, whereas the activity of lecithin cholesterol acyl transferase was significantly increased in the plasma of hypertensive rats. Docking result showed the interaction between sinapic acid and HMG-CoA reductase. Sinapic acid has shown best ligand binding energy of -5.5 kcal/M. Moreover, in chick embryo model, sinapic acid improved vessel density on chorioallantoic membrane. These results of the present study concludes that sinapic acid acts as a protective agent against hypertension associated cardiac dysfunction, kidney fibrosis and lipid alterations.

Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation.

In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling.

Sinapic acid protects heart against ischemia/reperfusion injury and H9c2 cardiomyoblast cells against oxidative stress.

The present study was designed to evaluate antioxidant and cardioprotective potential of sinapic acid (SA) against ischemia/reperfusion (I/R) injury. Cardiac functional recovery after I/R was evaluated by percentage rate pressure product (%RPP) and percentage coronary flow (%CF). Myocardial injury was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining and LDH enzyme leakage. Oxidative stress was estimated by lipid peroxidation level. eNOS protein expression in reperfused heart was assessed using Western blot method. Finally, in order to support the antioxidant effect of SA, in vitro protective potential of SA was assessed on H2O2-induced oxidative stress in H9c2 cardiomyoblast cells. The overall results demonstrated that I/R induced cardiac dysfunction, injury and oxidative stress was attenuated by SA treatment. Moreover, in vitro results also shown that, SA protects H9c2 cells from oxidative stress and modulates mitochondrial membrane permeability transition (MPT). In conclusion, coupled results from both in vivo and in vitro experiments have confirmed that SA with antioxidant role protects cardiac cells and its functions from I/R induced oxidative stress.

Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats.

OBJECTIVES: Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling. METHODS: An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells. RESULTS: Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-ß, ß-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner. CONCLUSIONS: Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential.

Vanillic acid: a potential inhibitor of cardiac and aortic wall remodeling in l-NAME induced hypertension through upregulation of endothelial nitric oxide synthase.

The objective of the present study is to investigate the effects of vanillic acid on blood pressure, cardiac marker enzymes, left ventricular function and endothelial nitric oxide synthase (eNOS) expression in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), heart rate, cardiac marker enzymes and organ weight were increased. Impaired left ventricular function and decreased aortic eNOS expression was also observed in hypertensive rats. Moreover, treatment with vanillic acid exhibited beneficial effect on blood pressure, left ventricular function and cardiac marker enzymes. In addition, treatment with vanillic acid on hypertensive rats had upregulated eNOS expression and showed beneficial effects evidenced by histopathology and ultrastructural observations of aorta. In conclusion, vanillic acid has enough potential to normalize hypertension and left ventricular function in l-NAME induced hypertensive rats. With additional studies, vanillic acid might be used as a functional drug or as an adjuvant in the management of hypertension.

Vanillic acid prevents the deregulation of lipid metabolism, endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats.

Hypertension is one of the main factors causing cardiovascular diseases. The present study was designed to evaluate the protective effect of vanillic acid against nitric oxide deficient rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220g, by oral administration of N(ω)-nitro-l arginine methyl ester (l-NAME) 40mg/kg in drinking water for 4 weeks. Vanillic acid was administered orally at a dose of 50mg/kg b.w. Nitric oxide deficient rats showed increased levels of mean arterial pressure (MAP), heart rate (HR) and decreased heart nitric oxide metabolites (NOx). A significant increase in the levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase in the plasma, liver and kidney and decreased level of high density lipoprotein-cholesterol (HDL-C) are observed, whereas there is a decrease in the activities of plasma lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) in nitric oxide deficient rats. l-NAME rats also showed an increase in TC, TG, FFA and PL levels in the liver and kidney tissues. Vanillic acid treatment brought the above parameters towards near normal level. Moreover the down regulated endothelial nitric oxide synthase (eNOS) and up regulated expression of endothelin 1 (ET1) components was also attenuated by vanillic acid treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that vanillic acid has enough potential to attenuate hypertension, dyslipidemia and hepatic and renal damage in nitric oxide deficient rats.

Valproic acid prevents the deregulation of lipid metabolism and renal renin-angiotensin system in L-NAME induced nitric oxide deficient hypertensive rats.

The present study was aimed to investigate the antihyperlipidemic and renoprotective potential of valproic acid against N(ω)-nitro-L arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), kidney weight, levels of oxidative stress markers in tissues were increased. Dyslipidemia was also observed in hypertensive rats. Moreover, enzymatic and nonenzymatic antioxidant network also deregulated in tissues. Valproic acid (VPA) supplementation daily for four weeks brought back all the above parameters to near normal level and showed no toxicity which was established using serum hepatic marker enzyme activities and renal function markers. Moreover the up regulated expression of renin-angiotensin system (RAS) components were also attenuated by VPA treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that VPA has enough potential to attenuate hypertension, dyslipidemia and renal damage in nitric oxide deficiency induced hypertension.

Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role.

Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic transdifferentiation of aortic VSMC in CRF rats.

Cardiovascular dysfunction and vascular calcification is the leading cause of death in chronic renal failure (CRF) patients. This study was designed to evaluate the effect of diosgenin on coronary flow resistance and to address the question whether the previously proven antivascular calcification potential of diosgenin is associated or not with the osteochondrogenic transdifferentiation of vascular smooth muscle cells (VSMC). In this study, CRF in Wistar rats was induced by fed with 0.75% adenine and diosgenin was treated everyday at the dose of 40 mg/kg. Langendorff based isolated heart protocol was employed to analyze the coronary flow resistance. Western blot method was used to explore the phosphorylation dynamics of endothelial nitric oxide synthase (eNOS) at the serine 1177 residue. In addition, cardiac nitric oxide metabolites level also assessed. Quantitative expression of VSMC and osteochondrogenic markers was also evaluated. Antioxidant potential of diosgenin was studied in vitro. The outcome of the present study explores that diosgenin treatment significantly improves the coronary resistance and increased the nitric oxide metabolites level compared with CRF. Further, diosgenin increases the phosphorylation of eNOS (peNOS ser1177). Moreover, diosgenin reduced the aortic expression of osteochondrogenic markers and improved the VSMC phenotype components. Further, diosgenin shows concentration dependent antioxidant potential. In conclusion, this study have proven that diosgenin have enough potential to improve the coronary function and interfere the osteochondrogenic transdifferentiation program of aortic VSMC which supports its antivascular calcification potential.

Diosgenin improves vascular function by increasing aortic eNOS expression, normalize dyslipidemia and ACE activity in chronic renal failure rats.

In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress in the development of cardiovascular diseases has been highlighted. The aim of the present study is to evaluate the effect of diosgenin, an antioxidant on chronic renal failure (CRF) induced vascular dysfunction. CRF was induced by feeding the rats with a diet containing 0.75 % adenine and diosgenin was given orally (everyday at the dose of 40 mg/kg). Isometric force measurement was performed on isolated aortic rings in organ baths. Levels of reduced glutathione (GSH), nitric oxide metabolites, and endothelial nitric oxide synthase mRNA in rat aorta were examined. Further, plasma lipid profile, activity of enzymes of lipid metabolism, and aortic angiotensin converting enzyme (ACE) also studied. The overall results have proved that diosgenin attenuates CRF-induced impairment in acetylcholine induced endothelium-dependent and sodium nitroprusside induced endothelium-independent vascular relaxation. Moreover, it elevates the GSH and restores the eNOS mRNA expression level. CRF-induced dyslipidemia and ACE activity was also inhibited by diosgenin treatment. This study indicates that diosgenin have enough potential to protect vasculature against oxidative stress, dyslipidemia which in turn improves the vascular function in CRF milieu.

Diosgenin attenuates vascular calcification in chronic renal failure rats.

Vascular calcification due to elevated phosphate levels is the major contributor of cardiovascular dysfunction. The oxidative stress and gene expression events modulate the transdifferentiation of vascular smooth muscle cells into osteogenic phenotype. This present study intends to evaluate the dose-dependent effect of diosgenin, an antioxidant on high phosphate induced vascular calcification in adenine-induced chronic renal failure rats. High phosphate environment causes elevated calcium accumulation with related histological changes and alkaline phosphatase activity in aorta. Further it downregulates the activity of enzymatic antioxidants and elevates the level of lipid peroxidative markers. Moreover, the renal failure leads to reduced nitric oxide production. But, treatment with diosgenin at a dose of 10, 20, and 40 mg/kg given via oral gavages causes reversion of all the above events in a dose-dependent manner. The highest dose has shown more potential activity than other two doses, which has the ability to protect the alteration of liver markers and red blood cell antioxidant system without any adverse effects and it does not alter the kidney associated changes too. Finally, the Fourier transform infrared spectroscopy study strongly supports its ability to protect the macromolecules from oxidative stress. All the above evidences show that diosgenin has overall benefits against renal failure-induced vascular calcification-associated oxidative stress.

Syringic acid ameliorates (L)-NAME-induced hypertension by reducing oxidative stress.

The objective of the present study was to investigate the effects of syringic acid (SA), a phenolic acid, on N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats by oral administration of L-NAME (40 mg/kg/day) dissolved in drinking water daily for 4 weeks. Rats were treated with different doses of SA (25, 50, and 100 mg/kg body weight (b.w.)). Systolic blood pressure of control and experimental rats was recorded. Plasma nitric oxide metabolites (NOx), lipid peroxidative products such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione were estimated in erythrocytes, plasma, and tissues of experimental rats. Hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and renal functional markers such as urea, uric acid, and creatinine were also estimated in serum. The increased levels of blood pressure, lipid peroxidation products, hepatic and renal function markers, and the decreased level of NOx and antioxidants in L-NAME-induced hypertensive rats were reversed upon SA treatment. The protective effect at the dose of the three tested doses (25, 50, and 100 mg/kg) of SA at a dose of 50 mg/kg b.w. exerts optimum protection. Biochemical findings are substantiated by the histological observation. The protective effects of SA are mediated by reducing oxidative stress and retaining the bioavailability of NO in the cardiovascular system.

The flavonoid morin restores blood pressure and lipid metabolism in DOCA-salt hypertensive rats.

OBJECTIVE: This study was undertaken to investigate the antihypertensive and antihyperlipedimic potential of morin against deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Hypertension was induced in uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA (25 mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. Morin (50 mg/kg) was administered to DOCA-salt rats orally using an intragastric tube daily for a period of 6 weeks. RESULTS: The DOCA-salt hypertensive rats showed significant elevation in mean arterial pressure (MAP), heart rate (HR) and reduction in body weight. A significant increase in the concentrations of plasma and tissue (liver, kidney, heart, and aorta) lipids such as total cholesterol, triglycerides, free fatty acids, phospholipids, plasma low-density and very low-density lipoproteins cholesterol, and a decrease in the concentration of high-density lipoprotein cholesterol were noticed in DOCA-salt hypertensive rats. Also, the levels of urinary protein and the activity of 3-hydroxy 3-methylglutaryl coenzyme A reductase in the plasma and tissues were increased, and lecithin cholesterol acyl transferase activity in the plasma was decreased in DOCA-salt rats. Morin supplementation (50 mg/kg) throughout the experimental period restored all the above parameters significantly. CONCLUSION: Morin has a potential role in attenuating severe hypertension and hyperlipedimia.

Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet.

An investigation was made to reveal the protective effects of veratric acid (VA), a phenolic acid against atherogenic diet-induced hyperlipidemic rats. Male albino Wistar rats were fed with atherogenic diet (4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil) daily for 30 days and treated with VA (40 mg/kg body weight) daily for a period of 30 days. Rats fed with atherogenic diet showed significant (P < 0.05) elevation in the level of plasma lipids, systolic and diastolic blood pressure, oxidative stress markers (thiobarbituric acid reactive substances, lipid peroxides) and significant (P < 0.05) reduction in the activities of enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin C, vitamin E, and reduced glutathione) antioxidants in erythrocytes, plasma, and tissues (liver, kidney, and aorta). Oral administration of VA (40 mg/kg body weight) for 30 days to atherogenic diet fed rats markedly attenuates systolic, diastolic blood pressure and lipid peroxidation products. Further, VA treatment significantly improved enzymatic and non-enzymatic antioxidants levels and showed beneficial effects on lipid profile in atherogenic diet rats. All the above alterations were supported by histopathological observations. These results indicate that oral administration of VA ameliorates atherogenic diet-induced hyperlipidemia in rats by its free radical scavenging; improving the antioxidants and lipid lowering properties.

Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: a biochemical and histopathological evaluation.

The present study was designed to evaluate the antihypertensive and antioxidant effect of morin, a flavonoid against deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA (25mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. The DOCA-salt hypertensive rats showed significant (P < .05) increase in the systolic and diastolic blood pressure, heart rate, water intake and organ weights (kidney, heart, aorta and liver). DOCA-salt hypertensive rats also showed significant (P < .05) increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes in plasma and tissues (kidney, heart, aorta and liver), and significant (P < .05) decrease in the body weight, nitrite and nitrate levels in plasma and heart. Furthermore, the activities of enzymic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of non-enzymic antioxidants such as reduced glutathione, vitamin C and vitamin E in plasma and tissues were significantly (P < .05) decreased in DOCA-salt rats. Morin supplementation (50mg/kg) daily for six weeks brought back all the above parameters to near normal level. The above findings were confirmed by the histopathological examination. No significant (P < .05) effect was observed in UNX-rats treated with morin (50mg/kg). These results suggest that morin acts as an antihypertensive and antioxidant agent against DOCA-salt induced hypertension.

Effect of veratric acid on the cardiovascular risk of L-NAME-induced hypertensive rats.

Hypertension is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220 g, by oral administration of L-NAME (40 mg/kg) in drinking water for 4 weeks. Rats were treated with VA (40 mg/kg) for 4 weeks. L-NAME-treated rats showed significant increase in mean arterial pressure and heart rate. A significant increase in the concentrations of plasma, tissue (liver and kidney) lipids, and lipoproteins and a significant decrease in the concentration of high-density lipoprotein cholesterol were noticed in L-NAME-induced hypertensive rats. The activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly in the liver and kidney, whereas the activities of lipoprotein lipase and lecithin cholesterol acyl transferase were decreased significantly in the plasma of hypertensive rats. Histopathology of liver and kidney and in vitro study also confirmed the biochemical findings of this study. Thus, oral administration of VA reduced hyperlipidemia related to the risk of hypertension.

Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats.

The present study was aimed to evaluate the antihypertensive effect of diosmin in deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/kg body weight) and 1% NaCl in the drinking water for six consecutive weeks. The important pathological events that occurred in DOCA-salt treated rats were significant increase in systolic, diastolic blood pressure, sodium and chloride in serum and lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) in plasma and tissues (liver, kidney, heart and aorta) and significant decrease in serum potassium, total nitrite and nitrate levels in plasma. The activities of hepatic aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and the levels of renal urea, uric acid, creatinine in serum, water intake, and organ weight (kidney and heart) were significantly increased in DOCA-salt hypertensive rats. DOCA-salt treated rats also showed a significant decrease in body weight, activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of reduced glutathione, vitamin C and vitamin E in plasma and tissues. Treatment with diosmin (25, 50 and 100 mg/kg body weight) brings back all the above parameters to near normal level, in which 50 mg/kg body weight showed the highest effect than that of other two doses. Histopathology of heart and kidney also confirmed the protective effect of diosmin. Thus the experiment clearly showed that diosmin acts as an antihypertensive agent against DOCA-salt induced hypertension.

Molecular metabolic fingerprinting approach to investigate the effects of borneol on metabolic alterations in the liver of nitric oxide deficient hypertensive rats.

Hypertension is one of the major risk factor that underlie a wide range of cardiovascular irregularities which causes functional and metabolic alterations in vascular system and major organs. Nitric oxide is the central regulator of the vascular system and its deficiency leads to increased blood pressure and metabolic alterations in liver. Fourier transform infrared spectroscopy (FTIR) is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds with in the sample that absorbs it and different samples contain diverse configurations of molecular bonds. Both wavenumber and area of the vibrational spectra can be used to explore the qualitative and quantitative constituent of macromolecules. In this study, we intended to evaluate the protective role of borneol, a natural terpene on liver metabolism in a nitric oxide deficient model of hypertension through interpretation of FTIR spectral information. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The over all findings demonstrate that in nitric oxide deficient animal model of hypertension, the liver metabolic program is altered through increasing the structural modification in proteins and triglycerides, and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected by borneol in liver and showed its ability to exert a novel defensive action on hepatic metabolism.