Una-Jovana Vajic

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.

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 < 0.05) compared to AKI control. It also increased cardiac output and catalase activity (P < 0.05). Lipid peroxidation and renal vascular resistance were decreased in TEMPOL (P < 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 O2 − scavenging.

Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

Abstract 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.

[PP.09.11] TEMPOL SUPPLEMENTATION DOES NOT OVERCOME BENEFICIAL EFFECT OF LOSARTAN IN HYPERTENSIVE RATS WITH EARLY COURSE OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Objective: Previously, we demonstrated that losartan had beneficial effect on renal function and structure in spontaneously hypertensive rats (SHR) with early course of adriamycin (ADR) nephropathy. Here, the aim was to investigate whether combination of losartan (L) with tempol (T), a membrane-permeable radical scavenger, could overcome this beneficial effects in the early course of ADR-induced focal segmental glomerulosclerosis (FSGS). Design and method: Females SHR (24-week-old) were divided in four groups. Control rats (SHC) received vehicle, while SHADR, SHADR+L, SHADR+L+T groups received ADR (2 mg/kg body weight i.v.) twice in 3-week-interval. After the second injection, SHADR+L received L (10 mg/kg/day), SHADR+L+T received L+T (10+100 mg/kg/day), while SHADR and SHC received tap water (by gavage) for 6 weeks. At the end of the experiment, albuminuria, kidney antioxidant enzymes activities (SOD-superoxide dismutase, catalase, and GPx-glutathione peroxidase) and histology were analyzed. Results: Albuminuria was significantly increased in SHADR group compared to control (p < 0.01). Losartan reduced albumin excretion to a value not significantly different from control. However, after combined L+T-treatment albuminuria remained significantly higher than in SHC (p < 0.05). SOD and GPx activities were diminished in ADR-treated SHR (p < 0.001). Losartan significantly improved these changes, and reverted SOD and GPx activities to the level as in control. Combined treatment failed to change SOD, while GPx activity became significantly decreased (p < 0.01) compared to both, SHADR+L and SHC groups. Adriamycin did not affect catalase activity, but chronic losartan or combined treatment significantly increased catalase activity compared to control. Glomerular sclerosis was significantly increased in SHR after ADR application (p < 0.001), and losartan alone, or in combination with tempol, did not alter it. ADR-induced tubular injury was significantly reduced after losartan treatment (p < 0.01) compared to SHADR. Conversely, in SHADR+L+T group tubular damage was similar to that of SHADR, and significantly elevated versus both, SHADR+L and SHC. Conclusions: Our results showed that combined treatment with tempol and losartan failed to improve kidney function, structure and antioxidant enzymes activities in experimental FSGS. Therefore, tempol supplementation does not overcome beneficial effect of losartan in hypertensive rats with early course of ADR-induced FSGS.

[PP.31.12] EFFECTS OF REGULAR CONSUMPTION OF RED WINE AND ALCOHOL-FREE RED WINE ON SYSTEMIC HAEMODYNAMICS, LIPID PROFILE AND OXIDATIVE STRESS IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Numerous studies have shown that moderate wine consumption is associated with decreased incidence of cardiovascular disease, including hypertension. Other studies have observed that moderate alcohol consumption lowers the risk of cardiovascular events. The aim of the present study was to compare the effects of regular red wine (RW) and alcohol-free red wine (AFRW) consumption (1 ml/day) on systemic haemodynamics, lipid profile and oxidative stress in adult male spontaneously hypertensive rats (SHR). Design and method: Control SHRC group (n = 8), received tap water, SHR+RW (n = 8) received red wine (Prokupac wine, Cellar Braca Rajkovic, Serbia) and SHR+AFRW (n = 8) received alcohol-free red wine by gavage throughout the 4-week experimental period. Systolic (SBP), diastolic (DBP), mean blood pressure (MBP), heart rate (HR), cardiac index (CI) and total vascular resistance (TVR) were measured in anesthetized rats. Blood samples were collected for total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins (LDL) cholesterol, bilirubin, uric acid and plasma TBARS (p-thiobarbituric acid reactive substances). Results: SBP was found to be lower in SHR+AFRW and SHR+RW groups compared to control. Chronic consumption of AFRW resulted in a significant decrease of DBP and MAP (p < 0.05), while chronic RW application significantly reduced only the DBP. None of the two types of wine had significant effect on HR, CI and TVR of SHRs. The lipid profile was significantly changed in SHR after RW but not after AFRW consumption. RW raise the level of total cholesterol (p < 0.05) relative to control, and the triglycerides were increased compared to the control as well as the AFRW group (p < 0.001). Although, HDL was slightly higher and LDL cholesterol was mildly to moderately lower in both wine groups compared to control. AFRW doubles the production of endogenous antioxidant bilirubin in the SHRs, while RW cause a significant increase of plasma uric acid (p < 0.05) compared to control. Both, RW and AFRW, significantly reduced p-TBARS. Conclusions: Chronic intake of AFRW has a better effect on blood pressure and lipid proifile of SHR than consumption of RW. Both, RW and AFRW, can increased antioxidant capacity and reduce susceptibility of SHR plasma to lipid peroxidation.

[PP.31.13] HAEMODYNAMIC DOSE-DEPENDENT RESPONSE TO OLIVE LEAF EXTRACTS IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Numerous studies demonstrate that a Mediterranean diet leads to significant drops in elevated blood pressure. It is well known that different products of Olea europea L. are very important part of this diet. The aim of our study was to investigate the dose-dependent response of haemodynamic parameters to olive leaf extracts in SHR Design and method: Experiment was performed in anesthetized, six-month-old male spontaneously hypertensive rats (SHR). SHR were divided into 3 experimental groups: the group treated with 5 mg/kg of olive leaf extract (OE5; n = 8); the group treated with 25 mg/kg of olive leaf extract (OE25; n = 8); and the group treated with 50 mg/kg of olive leaf extract (OE50; n = 7). Different dosage of olive leaf extract was given by bolus, through the jugular vain. Mean arterial pressure (MAP), cardiac output (CO), heart rate (HR) were measured, and total peripheral vascular resistance (TPVR) was calculated before and after bolus. Results: Figure. No caption available. Conclusions: Our results suggest that dosages of 25 mg/kg and 50 mg/kg olive leaf extract lower blood pressure in SHR, but in two different ways. Lower dosage decreases MAP due to vascular response (decreases TPVR), and higher dosage decreases MAP because of cardiac response due to decrease of CO.