Summary

As wine polyphenols were shown to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to affect it. Lipid peroxidation was evaluated by determination of thiobarbituric acid-reactive substances. Vascular function was assessed in rings of the femoral artery using Mulvany-Halpern’s myograph. Maximal endothelium-dependent acetylcholine (ACh)-induced relaxation was reduced in control SHR vs. WKY rats by approximately 9.3 %, which was associated with a significant decrease of its NO-independent component. AWE failed to affect maximal ACh-induced relaxation, both its NO-dependent and independent components, compared to controls of the same genotype. AWE however reduced lipid peroxidation in the left ventricle of both WKY and SHR and in the liver of SHR. In conclusion, three-week administration of AWE failed to reduce BP and to improve endothelial function in the femoral arteries of both genotypes investigated. Key word

Vascular Effects of Red Wine Polyphenols in Chronic Stress-Exposed Wistar-Kyoto Rats

Summary Present study investigated the effect of red wine polyphenolic compounds (Provinols TM ) on blood pressure (BP), nitric oxide synthase (NOS) activity and vascular function in Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding. Adult male rats were divided into four groups: control (480 cm 2 /rat), Provinols TM -treated (20 mg/kg/day, 480 cm 2 /rat), crowded (200 cm 2 /rat) and crowded treated with Provinols TM (20 mg/kg/day, 200 cm 2 /rat) for 8 weeks. No differences in BP were observed among the groups at the end of experiment, however, reduced BP was observed in Provinols TM -treated rats after 3 weeks of treatment. NOS activity in the aorta was significantly elevated in crowded rats, while Provinols TM alone had no effect on nitric oxide (NO) production. Acetylcholine-induced relaxation of the femoral artery was significantly improved in stressed and Provinols TM -treated rats vs. control, without significant changes in their noradrenaline-induced vasoconstriction. Interestingly, Provinols TM blunted the elevation of NO production and vasorelaxation during crowding. Increased endothelium-dependent vasorelaxation and NO synthesis in crowded rats may represent the adaptation mechanisms, resulting in unaltered blood pressure in stress-exposed normotensive rats. This study further demonstrated that elevated release of NO during chronic stress may be prevented by Provinols TM. Thus, Provinols TM might maintain equilibrium between endothelium-derived vasoconstrictor and vasodilator factors in stress

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental

Protection of the vascular endothelium in experimental situations

One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo

Summary

This study examined nitric oxide (NO) production, oxidative load and endothelium-dependent relaxation (NO-dependent and NOindependent) in adult male borderline hypertensive (BHR) and spontaneously hypertensive (SHR) rats as compared to normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined by tail-cuff. NO production was determined by conversion of [ 3 H]-L-arginine. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured for assessment of oxidative load. Vascular function was investigated in rings of the femoral artery (FA) using a wire myograph. BP of WKY, BHR and SHR was 106±2, 143±3 and 191±3 mm Hg, respectively (p<0.01 for each). Significant left ventricle (LV) hypertrophy and elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared to WKY. NO production was elevated significantly i

Media 3: Three-dimensional structure of a single colloidal crystal grain studied by coherent x-ray diffraction

Originally published in Optics Express on 13 February 2012 (oe-20-4-4039

Media 1: Three-dimensional structure of a single colloidal crystal grain studied by coherent x-ray diffraction

Originally published in Optics Express on 13 February 2012 (oe-20-4-4039

Nitric oxide synthase blockade and body fluid volumes

The influence of chronic nitric oxide synthase inhibition with N G-nitro-L-arginine methyl ester (L-NAME) on body fluid distribution was studied in male Wistar rats weighing 260-340 g. Extracellular, interstitial and intracellular spaces, as well as plasma volume were measured after a three-week treatment with L-NAME (~70 mg/kg per 24 h in drinking water). An increase in extracellular space (16.1 ± 1.1 vs 13.7 ± 0.6 ml/100 g in control group, N = 12, P<0.01), interstitial space (14.0 ± 0.9 vs 9.7 ± 0.6 ml/100 g in control group, P<0.001) and total water (68.7 ± 3.9 vs 59.0 ± 2.9 ml/100 g, P<0.001) was observed in the L-NAME group (N = 8). Plasma volume was lower in L-NAME-treated rats (2.8 ± 0.2 ml/100 g) than in the control group (3.6 ± 0.1 ml/100 g, P<0.001). Blood volume was also lower in L-NAME-treated rats (5.2 ± 0.3 ml/100 g) than in the control group (7.2 ± 0.3 ml/100 g, P<0.001). The increase in total ratio of kidney wet weight to body weight in the L-NAME group (903 ± 31 vs 773 ± 45 mg/100 g in control group, P<0.01) but not in total kidney water suggests that this experimental hypertension occurs with an increase in renal mass. The fact that the heart weight to body weight ratio and the total heart water remained constant indicates that, despite the presence of high blood pressure, no modification in cardiac mass occurred. These data show that L-NAME-induced hypertension causes alterations in body fluid distribution and in renal mass