Uticaj endotelina i L-NAME na koncentraciju mokraćne kiseline i uree u plazmi kod Wistar pacova

Effects of endothelins, which include vasoconstriction and vasodilatation are possible by different molecular mechanisms. Endothelins induce increased synthesis of nitric oxide which in turn inhibits the synthesis of endothelin. Changes in biochemical parameters connected with the increased and decreased synthesis of nitric oxide are not thoroughly examined yet. In a series of experiments we compared the effects of endothelin (ET-1) on the inhibition of nitric oxide synthase (NOS), as well as the effects of L-nitro arginin metal estar (L-NAME) on plasma urea and uric acid concentration. Experiments were performed on anesthetized female adult Wistar rats. The experimental groups received an i. v. bolus of ET-1, L-NAME or saline. All parameters, heamodynamic and biochemical, were measured before the animals were sacrificed. L-NAME increased the mean arterial pressure, decreased renal blood flow and increased vascular resistance in carotid and renal arteries and increased in plasma uric acid and urea concentrations. ET- 1 significantly decreased uric acid concentration in the plasma but did not effect plasma urea concentration compared to the control group. These differences show complex relations of nitric oxide with cellular signalization compared to the basic NO-cGMP pathway.Efekti endotelina koji uključuju vazokonstrikciju I vazodilataciju ostvaruju se različitim molekularnim mehanizmima. Endotelin indukuje povećanu sintezu azotnog oksida za koji se smatra da povratno inhibira sintezu endotelina. Promene biohemijskih parametara vezanih za povećanu i smanjenu sintezu NO nisu dovoljno proučene. U ovom radu su upoređeni efekti endotelina (ET-1) i inhibitora NOS-a, L-NAME na koncentraciju mokraćne kiseline i uree u plazmi. Eksperimenti su izvedeni na anesteziranim odraslim NW pacovima, ženskog pola. Eksperimentalne životinje su u i.v. bolusu primale ET-1, L-NAME ili fiziološki rastvor. Svi hemodinamski i biohemijski parametri su mereni pre žrtvovanja. L-NAME dovodi do povećanja srednjeg arterijskog pritiska smanjenja renalnog protoka i povećanja vaskularnog otpora u karotidnoj i renalnoj arteriji i povećanja koncentracije mokraćne kiseline i uree u plazmi. ET-1 značajno smanjuje koncentraciju mokraćne kiseline u plazmi ali ne utiče na koncentraciju uree u odnosu na kontrolu. Ove razlike pokazuju kompleksnije relacije NO-a sa ćelijskom signalizacijom u odnosu na osnovni NO-cGMP put

Effects of high dose olive leaf extract on the hemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats

The antihypertensive activity of olive leaf extract (OLE), a natural antioxidant is recognized, but its influence on the cardiovascular system when administered in a high dose has not yet been investigated. The aim of the present study was to determine the acute effects of excessive intake of standardized OLE on blood pressure, heart rate and oxidative status in both spontaneously hypertensive rats and normotensive Wistar rats. The systolic arterial pressure and heart rate were measured using a tail-cuff and pneumatic pulse detector before and 60 and 120 min after intragastric OLE administration. The activities of catalase, glutathione peroxidase, superoxide dismutase (SOD) and glutathione reductase in erythrocytes, as well as lipid peroxidation in plasma (pTBARS) were measured spectrophotometrically at the same time points. A high-dose of OLE did not influence blood pressure, heart rate or pTBARS in normotensive rats, while the SOD, catalase and glutathione reductase activities were significantly increased. The same dose significantly decreased blood pressure in hypertensive rats, but increased the pTBARS and SOD activity. Excessive oral intake of OLE induced moderate hypotensive effects only in spontaneously hypertensive rats, suggesting the absence of harmful hemodynamic effects after an oral overdose in both rat strains. However, its pro-oxidative role when given in a high dose in hypertensive organisms should not be neglected

Optimization of the extraction of antioxidants from stinging nettle leaf using response surface methodology

The aim of this study was to optimize the parameters for the extraction of total flavonoids from stinging nettle leaf. Comparison of the effects of different solvents on total flavonoid content showed that, regardless of extraction time, aqueous methanolicextracts had higher total flavonoid content than did aqueous ethanolic extracts. So, full factorial design and response surface methodology (RSM) were em-ployed to estimate the effects of methanol content (50, 75and 100%) and extraction time (30, 60and 90 min) on the total flavonoid content and antioxidant capacities of the extracts. RSM analysis showed that methanol content in the solvent influenced significantly total flavonoid content and FRAP (ferric-reducing antioxidant power) antioxidant capacity, while extraction time had no significant effect on either of these responses. Extraction parameters for maximal total flavonoid content were estimated to be 69% aqueous methanol and 67 min, and 65% aqueous methanol and 83 min for maximal FRAPantioxidantcapacity. DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant capacity was not significantly affected by extraction time or methanol percentage in the solvent

Uticaj hronične promene vrednosti hematokrita na krvni pritisak i glomerulsku filtraciju kod pacova sa urođenom hipertenzijom

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.Brojna ispitivanja izvedena na životinjama i ljudima su ukazala da je povećanje viskoznosti krvi u direktnoj vezi sa hipertenzijom. Cilj naše studije je bio da se istraži uticaj promene vrednosti hematokrita (Hct) na krvni pritisak i funkciju bubrega u urođenoj hipertenziji. U tom cilju, istraživan je uticaj hroničnog povećanja ili smanjenja vrednosti Hct na hemodinamske parametre, vaskularnu reaktivnost, glomerulsku filtraciju i krivu bubrežne funkcije kod pacova sa urođenom hipertenzijom (SHR). Rezultati naše studije su ukazali da hronično povećanje vrednosti Hct dovodi do povećanja arterijskog krvnog pritiska (AKP) i perifernog vaskularnog otpora (PVO) kod SHR . Nasuprot tome, hronično smanjenje vrednosti Hct dovodi do smanjenja AKP i PVO, praćenih povećanjem minutnog volumena srca. Obe promene vrednosti Hct dovode do smanjenja vaskularne reaktivnosti. Hronično smanjenje vrednosti Hct izaziva nastanak akutne bubrežne insuficijencije. Ekskrecija natrijuma je pomerena ka većim vrednostima krvnog pritiska kod pacova sa povećanim vrednostima Hct, a ka nižim kod pacova sa sniženim vrednostima Hct. Hronično povećanje vrednosti Hct dovodi do razvoja maligne hipertenzije kod SHR. Potrebne su dalje studije da bi se utvrdio tačan stepen i priroda oštećenja bubrega nakon hronične promene vrednosti Hct

Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

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

Uticaj blokade receptora tip 1 za angotenzin II udružene sa uklanjanjem superoksidnog anjona na postishemični bubreg kod pacova sa urođenom hipertenzijom

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

Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats

Limited numbers of studies include research of microvibration therapy in experimental models. We examined effects of chronic vibroacustic-microvibration treatment on haemodynamics and anti-oxidative defense in experimental hypertension. Study was performed on chronically treated hypertensive and normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO), renal blood flow (RBF), glomerular filtration and activity of anti-oxidative enzymes were determined after three weeks treatment. Vibroacustic treatment had no influence on MAP and CO, but RBF was increased in both groups of treated rats. Additionally, vibroacustic treatment enhanced diuresis and increased glomerular filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was elevated in both treated rat strains, but activity of superoxide dismutase was unchanged. We conclude that microvibration treatment doesn't ameliorate hypertension but improves renal blood supply (trough diminished renal vascular resistance), glomerular filtration, diuresis, and enhances glutathione dependent anti-oxidant defense with more important beneficials in hypertensive animals

Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

Acute kidney injury (AKI) is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance (P lt 0.05) compared to AKI control. It also increased cardiac output and catalase activity (P lt 0.05). Lipid peroxidation and renal vascular resistance were decreased in TEMPOL (P lt 0.05). Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O-2(-) scavenging

Highly potent antioxidant olea europaea l. Leaf extract affects carotid and renal haemodynamics in experimental hypertension: the role of oleuropein

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

Upregulation of Heme Oxygenase-1 in Response to Wild Thyme Treatment Protects against Hypertension and Oxidative Stress

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