Chronic social stress increases nitric oxide-dependent vasorelaxation in normotensive rats
The aim of this study was to examine oxidative load and endothelium-dependent vasorelaxation in the serotonin pre-constricted femoral artery (FA) of Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding in the presence or absence of ascorbic acid (AsA) in working solution. Adult male rats were randomly divided into control (living space: 480 cm2/rat) or stressed (living space: 200 cm2/rat) groups for 8 weeks. Blood pressure and heart rate, determined using tail-cuff plethysmography, were not influenced by stress vs. control. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured in the left ventricle and liver (for assessment of oxidative load) and were found unchanged by chronic crowding. The nitric oxide (NO)-dependent component of endothelium-dependent relaxation was investigated in the FA using a wire myograph. In both the presence and absence of AsA, acetylcholine-induced relaxation of the FA of stressed rats significantly exceeded that of the controls, which was associated with an increase of the NO-dependent component. In conclusion, the data showed that chronic crowding did not produce oxidative stress in the organs investigated and indicate that elevation of NO production during chronic stress is an important way of adaptation, which may prevent normotensive rats from the development of stress-induced hypertension.
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.
In various areas of the bio-medical, pharmacological and psychological research a multitude of behavioural tests have been used to investigate the effects of environmental, genetic and epi-genetic factors as well as pharmacological substances or diseased states on behaviour and thus on the physiological and psycho-social status of experimental subjects. This article is reviewing the most frequently used behavioural tests in animal research (open field, elevated plus maze, zero maze, and black and white box). It provides a summary of common characteristics as well as differences in the methods used in various studies to determine motor activity, anxiety and emotionality. Additionally to methodological aspects, strain, sex and stress-related differences as well as the involvement of nitric oxide in modulation of motor activity and anxiety of rodents were briefly reviewed.
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.