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Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

Olive (Olea europaea L.) leaf extract (OLE) possesses powerful antioxidant, antihyperlipidemic, and anti-inflammatory properties. The aim was to investigated the effects of OLE on the hyperlipidemia, antioxidant defense, heme oxygenase/biliverdin reductase (HO/BVR) pathway, inflammation, and fibrosis in spontaneously hypertensive rats with focal segmental glomerulosclerosis (FSGS, a progressive form of chronic kidney disease) induced by adriamycin (2 mg/kg, i.v., twice in a 21-day period). Daily treatment of OLE (80 mg/kg, p.o.) for 6 weeks suppressed protein oxidation and lipid peroxidation (p lt .01 and p lt .001, respectively), significantly increased antioxidant enzymes activities and normalized antioxidant capacity, leading to the improvement of antioxidant defense independently of the HO/BVR pathway. Furthermore, the values of triglycerides (p lt .01), total, and low-density lipoprotein cholesterol (p lt .05, both) were improved by OLE. OLE strongly prevented glomerulosclerosis, interstitial inflammation, and fibrosis (renal injury score, FSGS: 8 +/- 0.45 vs. FSGS+OLE: 4.20 +/- 1.07; p lt .01), as evidenced by normalized fibronectin content (p lt .001), suppressed interstitial inflammatory cells infiltration and collagen deposition, without changing cytokines expressions. OLE decreased blood pressure with a tendency to reduce urine albumin loss. These data suggest that OLE may be effective in slowing down the progression of FSGS.

Oxidative damage to protein and lipid macromolecules in target organs in hypertension has been recognized as a major factor contributing to cardiovascular, cerebrovascular, and renal diseases. Data on protein and lipid oxidative damage in spontaneously hypertensive rats are numerous, but there is no information on DNA damage in tissues measured by comet assay. The aim of this study was to determine the baseline damage to DNA, protein, and lipid macromolecules in different organs of spontaneously hypertensive rats. Markers of lipid peroxidation, protein oxidation, and DNA damage were measured in blood, heart, kidney, and liver of 24-week-old spontaneously hypertensive rats. Plasma prooxidant and antioxidant status were determined as well. Age-matched normotensive Wistar rats were used as control. A rise in markers of lipid peroxidation and protein oxidation, malondialdehyde, and advanced oxidation protein products, was detected in all tissues of spontaneously hypertensive rats, with particularly high values in the liver. DNA damage, measured by the comet assay, was significantly higher in all the studied tissues of spontaneously hypertensive rats compared to normotensive control, with more severe damage in the cardiac and renal cells. Significant depletion of the plasma antioxidant barrier in spontaneously hypertensive rats was also observed. This study showed increased damage to all macromolecules in all studied samples of spontaneously hypertensive rats in comparison with control Wistar rats.

Background and Aims Oxidative stress is implicated in the pathophysiology of chronic kidney disease. Previously, we showed that adriamycin (anticancer agent, enhances reactive oxygen species production) induced focal segmental glomerular sclerosis (FSGS) with massive proteinuria in spontaneously hypertensive rats (SHR). The heme oxygenase (HO) system plays an important role in regulating oxidative stress and is protective in chronic kidney disease. HO-1 is a cytoprotective enzyme that catalyzes the conversion of highly reactive free heme molecules into biliverdin, carbon monoxide, and iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase and has potent antioxidant effect. Olive leaf extract (OLE, Olea europaea L.) is rich in phenolic compounds that are known to possess powerful antioxidant properties. Here, we aimed to investigate the effects of OLE, focusing on its modulatory role on oxidative stress and HO-1/BVR pathway in the kidney of SHR with adriamycin-induced FSGS. Method Adult females SHR were divided into three groups. Control rats received vehicle. Two other groups, FSGS and FSGS+OLE, received adriamycin (2 mg/kg body weight i.v.) twice in 3-week-interval. After the second injection, FSGS+OLE group received OLE (80 mg/kg/day) by gavage for 6 weeks. Mean blood pressure (MAP), urine albumin-to-creatinine (Ualb/cr), renal HO-1 and biliverdin reductase protein expressions (Western Blot), protein carbonyl content (PCOs), and antioxidant capacity (ABTS) were analyzed. Results In FSGS group albuminuria was significantly increased in comparison to the level in control. Chronic consumption of OLE markedly, but not significantly decreased Ualb/cr compared to that in control. Analysis of renal PCOs revealed that significant enhancement of protein oxidation in the kidney of model group was reduced after OLE treatment to the level as in control. The ABTS level in kidney homogenates significantly decreased in FSGS group in comparison to the level in control. OLE significantly increased renal antioxidant capacity in FSGS+OLE group compared to that in model group. Western blot analysis of HO-1, and biliverdin reductase in the kidney revealed that protein expressions of both enzymes were significantly decreased in FSGS group compared to that in control. Following OLE treatment in FSGS+OLE group protein expressions of HO-1, and biliverdin reductase remained at similar level as in model group. No change in MAP values were observed between control and model groups. OLE significantly decreased MAP in FSGS+OLE group in comparison to the value of model group, and nearly significant reduction of MAP compared to the value of control. Conclusion Collectively, our results showed that OLE expressed its antioxidant property and improved oxidative status in the kidney of SHR with ADR-induced FSGS, independently of the HO-1/BVR pathway.

The potential beneficial effects of chronic consumption of dried chokeberry fruit extract (DCE) were evaluated in the present in vivo study. The study concentrates on haemodynamic parameters, lipid profile and oxidative stress in spontaneously hypertensive rats. DCE was characterized by HPLC/DAD method and individual anthocyanins, phenolic acids, and flavonoids were determined. Four week administration of DCE, rich in polyphenols, especially anthocyanins, significantly reduced systolic (P lt 0.05), pulse pressure (P lt 0.05) compared to control group, probably via significantly increased diuresis (P lt 0.05). Significant decrease of plasma and erythrocytes TBARS was also found in the treated group. DCE consumption reduced lipid peroxidation through improving plasma FRAP reducing (P lt 0.01). The activity of SOD in the treated group had been significantly lower (P lt 0.01) compared to the control group. These results suggest that DCE could exert beneficial effects on cardiovascular health and has a potential as a nutritional supplement in arterial hypertension.

Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.

Numerous studies have shown that moderate wine consumption is associated with decreased incidence of cardiovascular disease, including hypertension. Others observed that moderate alcohol consumption lowers the risk of cardiovascular events. The aim of the present study was to identify and quantify the components of red wine (RW) and alcohol-free red wine (AFRW), and compare the effects of their 4-week consumption (1 mL/day) on haemodynamics, lipid profile and oxidative stress in adult male spontaneously hypertensive rats (SHR). Among anthocyanins, malvidin 3-O-glucoside dominates in both RW and AFRW. AFRW reduces blood pressure of SHR. Both RW and AFRW can increase antioxidant capacity and reduce susceptibility of plasma to lipid peroxidation. RW, due to adverse triacylglycerol levels elevates the risk of cardiovascular complications in SHR. Removing alcohol from wine eliminates these adverse effects and promotes AFRW as a useful beverage in hypertensive patients.

Background Urtica dioica L. (Stinging nettle) has been used for centuries for the treatment of numerous health issues. Purpose This study investigates the antioxidant capacity and the most abundant phenolic compounds of Urtica dioica L. leaf extract (UE), and its antihypertensive and antioxidative effects in vivo. Study design Spontaneously hypertensive rats were supplemented with 10, 50, and 200 mg/kg/day of UE and 10 mg/kg/day of losartan during 4-week period. Methods In this study, HPLC analysis of UE was performed, as well as the determination of antioxidant capacity, superoxide radical scavenging activity, and metal chelating ability. Hemodynamic parameters were measured directly in anesthetized rats. Also, antioxidant enzyme activity and concentration in erythrocytes were determined, as well as systemic oxidative stress and plasma antioxidant status. Results UE showed higher ferric reducing antioxidant power and Trolox equivalent antioxidant capacity than BHT, but lower than vitamin C. Furthermore, UE showed good metal chelating ability, but weak superoxide radical scavenging activity. All three tested UE doses managed to reduce systolic and diastolic blood pressure, as well as cardiac index, and to improve the antioxidative defense by increasing the activity of superoxide dismutase and catalase, without changing the concentration of the enzymes. Moreover, UE supplementation increased plasma antioxidant capacity and reduced systemic oxidative stress. Conclusion Chronic UE dietary supplementation had beneficial effects in the experimental model of essential hypertension.

Malignant hypertension is a severe form of hypertension which pathogenesis is not fully elucidated. The aim of our study was to investigate the role of Angiotensin II on hemodynamic and oxidative stress parameters in model of malignant hypertension by using losartan. Adult males were divided into three groups: normotensive Wister rats, control SHR and losartan treated SHR. Control and SHR group received a single bolus dosage of saline, while the SHR + LOS group received a losartan. Blood pressure, cardiac output, both total peripheral and carotid vascular resistance and carotid blood flow were measured. CAT, SOD and TBARS were determined in the blood samples. The treatment significantly decreased the blood pressure. There was no significant change in cardiac output or carotid blood flow, but treatment resulted in diminishment of vascular resistances, both total peripheral and carotid. There was a tendency to restore the values of SOD activity towards those of the normotensive group, but there were no change in CAT and TBARS levels. Taken together, our results show that a single application of losartan has a strong hypotensive effect. Angiotensin II seems to have a significant role in the malignant hypertension syndrome and it partially affects oxidative stress parameters. [Projekat Ministarstva nauke Republike Srbije, br. OI 175096]

Haemodynamic alterations in carotid and renal arteries are associated with the severity of target organ damage in patients with hypertension. Dietary habits, such as the Mediterranean diet, regulate blood pressure and oxidative stress, thus reduce the mortality rate due to cardiovascular diseases. In this study, our aim was to evaluate the reducing activity, antioxidant capacity and metal chelating ability of standardized Olea europaea L. leaf extract (OLE), and to test its (5, 25, 50 mg/kg) acute in vivo effects, as well as oleuropein's (OP, 10 mg/kg) on oxidative stress, carotid, renal and systemic haemodynamic parameters (blood pressure, heart rate, cardiac output, peripheral resistance) in spontaneously hypertensive rats (SHR). OLE has a higher antioxidative capacity than BHT, higher reducing ability than vitamin C, and 23 times lower capacity for metal ion chelation than EDTA. All three doses of OLE, and OP, improved oxidative stress in SHR. OLE5 improved carotid and renal haemodynamics, without significant effects on systemic haemodynamics. Two different mechanisms of antihypertensive responses to OLE were observed, OLE25 was most effective in reducing cardiovascular risks by improving systemic and regional (carotid and renal) haemodynamics, peripheral and regional vascular resistance. OLE50 causes the improvement of blood pressure and cardiac performances, but tends to retain elevated vascular resistance, therefore, reducing the inflow of blood into the brain and kidneys of the SHR. The OP did not alter systemic or regional haemodynamics, suggesting others constituents responsible for changes of cardiac function, as well as carotid and renal haemodynamics in response to OLE50.

Calf bronchopneumonia is complex multifactorial disease and for its accurate diagnosis and therapy, besides clinical examination, microbiologic, hematologic and biochemical analyses could be necessary. In general, additional analyses are not implemented, mainly because the disease biomarkers are not defined.To establish which analysis might be useful for determining the severity of the disease, we analyzed 23 three-month old calves with mild clinical signs of bronchopneumonia and 15 age-matched healthy calves.Pasteurella multocidawas isolated from deep nasal swabs of diseased calves. Peripheral blood erythrocyte and leukocyte count of bronchopneumonic and healthy calves showed no difference. Serum proteins, lipoproteins and lipids were analyzed with spectrophotometry, agarose gel electrophoresis, non-reducing SDS-PAGE, gel zymography, and thin-layer chromatography. The bronchopneumonic calves had an increased level of circulating immune complexes and α globulins, which contain some of the positive acute phase proteins. In diseased calves the increased concentration of total γ globulins (IgG), due to an increased concentration of anionic γ globulins (predominately IgG1), was detected. The increased concentration of anionic γ globulins followed by increased concentration of transferrin (negative acute phase protein) and HDL cholesterol, decreased concentration of LDL-cholesterol, unchanged activity of matrix metalloproteases and leukocyte counts might reflect the obvious absence of generalized inflammation. A positive correlation was found between the acquired results and the appearance of mild clinical signs. Therefore, we believe that the parameters analyzed in the peripheral blood could be applied as reliable disease markers to distinguish between severe (inflammatory) and mild forms of calf bronchopneumonia and to predict a better outcome for these calves.

Resveratrol the polyphenolic antioxidant molecule has been proposed as an effective agent in the prevention of several pathological conditions, thus this study was aimed to evaluate its chronic effects on functional and structural remodeling of the aorta in spontaneously (SHR) and malignantly hypertensive rats (MHR). Resveratrol significantly decreased arterial pressure and improved regional hemodynamic parameters, bioavailability of nitric oxide, ameliorated morphological changes in the tunica media and smooth muscle of the aorta, preserved endothelium, reduced inflammation and apoptosis in both SHR and MHR, but excrete more beneficial effects on SHR. Resveratrol suppressed lipid peroxidation, significantly improved oxidative status and reduced levels of lipids. These results suggest the cardiovascular benefits of resveratrol dietary enrichment in both experimental models of hypertension.

Down-regulation of nitric oxide synthase (NOS) and NO deficiency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T+L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were significantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a significant decline in the glomerular filtration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fibroblasts and myofibroblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD.

Hypertension is one of the main causes of cardiovascular disorders and since ancient times olive tree leaves have been used in its therapy. However the mechanisms of their atihypertensive effect have not been sufficiently explained yet. The main objective of our study was to investigate acute effect of olive tree leaves extract on haemodynamics and lipid peroxidation in rats with congenital hypertension under normal and blocked synthesis of nitric oxide. For the purpose of our research, there were used olive tree leaf extract EFLA® 943 as well as inhibitor of nitric oxide synthase enzyme L-NAME. Nitric oxide synthesis inhibition led to statistically significant increase of mean arterial pressure, reducing heart rate and cardiac output, increase of total vascular resistance and lipid peroxidation in plasma. Treatment by olive leaf extract led to decrease of mean arterial pressure, reducing the frequency and cardiac output, without change in lipid peroxidation. Olive leaf extract under blockade of nitric oxide led to decrease of mean arterial pressure, total peripheral resistance remained high, cardiac output low, and lipid peroxidation significantly increased. General conclusion is that olive leaf extract has a strong antihypertensive effect, decreases cardiac pre and after load and does not influence lipid peroxidation. Under blockade of nitric oxide synthesis, this extract keeps antihypertensive properties, but due to strong endothelial dysfunction, it is unable to regulate increased total peripheral resistance and marked lipid peroxidation. Hipertenzija je jedan od vodećih uzroka nastanka kardiovaskularnih oboljenja. Listovi masline se još od davnina koriste u lečenju hipertenzije, međutim mehanizmi njihovog antihipertenzivnog delovanja još uvek nisu dovoljno razjašnjeni. Glavni cilj naše studije bio je da ispitamo akutno dejstvo ekstrakta lista masline na hemodinamiku i lipidnu peroksidaciju pacova sa urođenom hipertenzijom u uslovima normalne i blokirane sinteze azotnog monoksida. Korišćeni su ekstrakt lista masline EFLA®943 i blokator enzima azot monoksid sintaze L-NAME. Blokada sinteze azotnog monoksida je dovela do statistički značajnog povećanja srednjeg arterijskog pritiska, smanjenja frekvence i minutnog volumena srca, povećanja ukupnog perifernog otpora i povećanja lipidne peroksidacije u plazmi. Tretman ekstraktom lista masline je doveo do sniženja srednjeg arterijskog pritiska, smanjenja frekvence i minutnog volumena srca, bez promena lipidne peroksidacije. Ekstrakt lista masline u uslovima blokade azotnog monoksida je doveo do sniženja srednjeg arterijskog pritiska, ukupni periferni otpor je ostao visok, minutni volumen nizak, a lipidna peroksidacija značajno povišena. Opšti zaključak je da ekstrakt lista masline iskazuje snažno antihipertenzivno dejstvo, smanjuje volemijsko i tenziono opterećenje srčanog mišića i ne menja stepen lipidne peroksidacije. U uslovima blokirane sinteze azotnog monoksida, ovaj ekstrakt zadržava antihipertenzivno svojstvo, ali usled izazvane snažne endotelne disfunkcije ne poboljšava sistemsku hemodinamiku i povećanu lipidnu peroksidaciju.

Ischemic acute kidney injury is characterized by renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and overproduction of angiotensin II and reactive oxygen species. Considering this complexity, the aim of our study was to investigate the effects of angiotensin II type-1 receptor blocker - Losartan and superoxide anion scavenger - Tempol, in a combined treatment on acute kidney injury in postischemic hypertensive rats. The experiment was performed in anesthetized, adult male spontaneously hypertensive rats. The right kidney was removed and the left renal artery was occluded for 40 minutes. Experimental groups received combined treatment (Losartan + Tempol) or saline in the femoral vein 5 minutes before, during and 175 minutes after clamp removal. Hemodynamics and biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. Histological examination was performed by optical microscopy. Combined treatment improves renal haemodynamics parameters which were exacerbated due to acute kidney injury. Acute kidney injury significantly decreased creatinine and urea clearance and increased lipid peroxidation in the plasma. Treatment with Losartan and Tempol induced a significant increase of creatinine and urea clearance. Lipid peroxidation in the plasma decreased and glutathione peroxidase enzyme activity in the erythrocytes increased after Losartan + Tempol treatment. This combined treatment reduced cortico-medullary necrosis and tubular dilatation in the kidney. Our results indicate that synergism of Losartan and Tempol treatment could have beneficial effects on blood pressure and kidney function, during postischemic acute kidney injury development in experimental hypertension. Glavne karakteristike ishemične akutne bubrežne slabosti su: renalna vazokonstrikcija, pad glomerulske filtracije, tubularna opstrukcija, vraćanje glomerulskog filtrata u intersticijum tubula i prekomerna produkcija angiotenzina II i reaktivnih vrsta kiseonika. Uzimajući u obzir kompleksnost ovog poremećaja, cilj ove studije je bio da istraži efekte kombinovanog tretmana blokatora angiotenzin II receptora tip 1 - Losartana i sakupljača superoksidnog anjona - Tempola u modelu ishemične bubrežne slabosti kod hipertenzivnih pacova. Eksperiment je urađen na odraslim anesteziranim mužjacima hipertenzivnih pacova. Desni bubreg je uklonjen, dok je na levoj renalnoj arteriji urađena okluzija u trajanju od 40 minuta. Eksperimentalne grupe su primile kombinovani tretman (Losartan+Tempol) ili fiziološki rastvor u femoralnu venu, 5 minuta pre i 175 minuta nakon uklanjanja kleme sa renalne arterije. Hemodinamski i biohemijski parametri su izmereni, a uzorci bubrega uzimani su 24 časa nakon reperfuzije. Histološka ispitivanja su rađena pomoću svetlosnog mikroskopa. Kombinovani tretman poboljšava renalnu hemodinamiku, poremećenu usled ishemične akutne bubrežne slabosti. U ovom modelu bubrežne slabosti dolazi do pada klirensa kreatinina i uree, i povećanja lipidne peroksidacije u plazmi.Tretman Losartanom i Tempolom dovodi do značajnog povećanja klirensa kreatinina i uree. Lipidna peroksidacija je smanjena, a aktivnost glutation peroksidaze u eritrocitima je povećana nakon kombinovanog tretmana sa Losartanom i Tempolom. Takođe, ovakav kombinovan tretman smanjuje kortiko-medularnu nekrozu i tubularnu dilataciju u bubregu. Naši rezultati ukazuju na to da sinergizam Losartana i Tempola može imati povoljan efekat na krvni pritisak i bubrežnu funkciju tokom razvoja postishemične akutne bubrežne slabosti u eksperimentalnoj hipertenziji.

High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure. Next product of heme oxidation, bilirubin (a chain-breaking antioxidant that acts as a lipid peroxyl radical scavenger), becomes significantly increased after wild thyme treatment and induces the reduction of plasma lipid peroxidation in hypertensive, but not in normotensive rats. The obtained results promote wild thyme as useful supplement for cardiovascular interventions.

Background. The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. Methods. Six-month-old female SHR were randomly selected in six groups. Two control groups (SH(6), SH(12)) received vehicle. Groups ADR(6), ADR+LOS(6) and ADR(12), and ADR+LOS(12) received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS(6) received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS(12) for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. Results. Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. Conclusion. Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to end-stage renal disease in SHR.

A full three level factorial design was implemented for optimization of extraction parameters in order to maximize total phenolic (TP) yield from stinging nettle leaf. Factors considered were percentage of methanol in solvent ( X 1 : 50–100% methanol) and extraction time ( X 2 : 30–90 min), and maceration was used as extraction method. A second-order polynomial model was applied for fitting experimental data and predicting the response, and this mathematical model produced a satisfactory fit ( R 2 = 0.993, p ˂ 0.01). The optimal extraction conditions were 54% aqueous methanol and 38 min extraction time, while maximal theoretical TP yield was 8.9 mg GAE/g DW. Solvent composition significantly affected extraction efficiency causing decrease of TP yield with increase of methanol percentage. On the other hand, extraction time did not influence significantly efficiency of extraction. Using LC/MS and HPLC analysis we detected and quantified three most abundant phenolic compounds: 2- O -caffeoyl malic acid, chlorogenic acid, and rutin. Comparison between maceration and ultrasound-assisted extraction (UAE) obtained extracts based on TP content as well as antiradical activity and HPLC results, showed that UAE have a better extraction capability affecting yield and time of extraction. Of all tested extracts, 54% aqueous methanolic extracts obtained with UAE and 38 min extraction time had the highest TP content.

The low incidence of cardiovascular disease in Mediterranean countries leads to an increased interest of the scientific community for the Mediterranean diet. Our aim was to evaluate total phenol and flavonoid contents, antioxidant capacity, free radical scavenging activity and potential antihypertensive effect of aqueous extract obtained from Thymus serpyllum L. (wild thyme, TE), an aromatic herb from the Lamiaceae family (highly present in Mediterranean diet), in spontaneously hypertensive rats (SHR) and in normotensive Wistar rats. Total phenol content of TE was 2008.33 +/- 10.6 mg/L GAE, and rosmarinic and caffeic acids were predominant phenolic compounds. The ferric reducing/antioxidant power and antioxidant capacity analysis revealed strong antioxidative properties of TE. In vitro nitric oxide-scavenging activity of 1 mg/l TE was 63.43 % with the IC50 value of 122.36 mu g/ml. Bolus injection of TE (100 mg/kg body weight i.v.) induced significant decrease of systolic and diastolic blood pressure and total peripheral resistance in SHR, without effects on these parameters in normotensive Wistar rats. Cardiac index remained unchanged after TE treatment in all experimental rats. Given dose of TE did not show significant nitric oxide-scavenging activity in vivo. Our results indicate that TE may protect against hypertension in experimental model of essential hypertension.

Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L, 10 mg/kg/day), tempol (T, 100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well astubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR.

Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR). Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite - lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.