Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia.

Brain hypoxia is involved in many diseases. The activation of angiogenesis is one of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In a previous work, we have shown that the adult rat striatum promotes angiogenesis in response to hypoxia via upregulation of the most important proangiogenic factor, the vascular endothelial growth factor (VEGF). However, the effects of hypoxia on angiogenesis in the aged striatum remain unknown and constitute our aim. Here we show the upregulation of hypoxia-inducible factor-1α in the striatum of aged (24-25 months old) Wistar rats exposed to acute hypoxia and analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA expression of the proangiogenic factors VEGF, transforming growth factor-ß1 (TGF-ß1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic control, no changes were detected at the protein level, showing an impaired response of these proangiogenic factors to hypoxia in the aged striatum. However, the striatal blood vessel network increased at 24 h of reoxygenation, suggesting that mechanisms independent from these proangiogenic factors may be involved in hypoxia-induced angiogenesis in the striatum of aged rats. A thorough understanding of the factors involved in the response to hypoxia is essential to guide the design of therapies for hypoxia-related diseases in the aged brain.

Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status?

OBJECTIVES: Fibromyalgia (FM) is a form of non-articular rheumatism characterised by chronic widespread musculoskeletal aching. Although some works have investigated the possible role of oxidative stress in the pathophysiology of FM, none has analysed a significant number of oxidative markers in the same patients. Consequently, we have performed an exhaustive study of the oxidative/antioxidative status in FM patients and healthy controls, as well as the relationship with FM clinical parameters. METHODS: In 45 female patients and 25 age-matched controls, we investigated the oxidative (lipid and protein peroxidation, and oxidative DNA damage) and antioxidative status (total antioxidant capacity (TAC), and antioxidant enzyme activities and compounds). Functional capacity and musculoskeletal pain were assessed by Fibromyalgia Impact Questionnaire (FIQ) and Visual Analogue Scale (VAS), respectively. The physical (PCS-12) and mental (MCS-12) health status was evaluated by SF-12. RESULTS: A significant increase in oxidative DNA damage and protein carbonyl content was found in FM patients vs. controls, as well as in antioxidant compounds such as copper and ceruloplasmin. Patients had diminished levels of TAC and zinc. Enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase were lower in FM patients. Significant correlations were observed in patients between oxidative DNA damage and MCS-12, and zinc and PCS-12. CONCLUSIONS: These findings reveal an imbalance between oxidants and antioxidants in FM patients. The lower antioxidant enzyme activities may lead to oxidative stress through the oxidation of DNA and proteins, which may affect the health status of FM patients.

Nitric oxide averts hypoxia-induced damage during reoxygenation in rat heart.

Nitric oxide (NO), synthesized by the hemoproteins NO synthases (NOS), is known to play important roles in physiological and pathological conditions in the heart, including hypoxia/reoxygenation (H/R). This work investigates the role that endogenous NO plays in the cardiac H/R-induced injury. A follow-up study was conducted in Wistar rats subjected to 30 min of hypoxia, with or without prior treatment using the nonselective NOS inhibitor L-NAME (1.5 mM). The rats were studied at 0 h, 12 h, and 5 days of reoxygenation, analysing parameters of cell, and tissue damage (lipid peroxidation, apoptosis, and protein nitration), as well as in situ NOS activity and NO production (NOx). The results showed that after L-NAME administration, in situ NOS activity was almost completely eliminated in all the experimental groups, and consequently, NOx levels fell. Contrarily, the lipid peroxidation level and the percentage of apoptotic cells rose throughout the reoxygenation period. These results reveal that NOS inhibition exacerbates the peroxidative and apoptotic damage observed before the treatment with L-NAME in the hypoxic heart, pointing to a cardioprotective role of NOS-derived NO against H/R-induced injury. These findings could open the possibility of future studies to design new therapies for H/R-dysfunctions based on NO-pharmacology.

Endogenous nitric oxide can act as beneficial or deleterious in the hypoxic lung depending on the reoxygenation time.

Nitric oxide (NO) has been implicated in many pathophysiological situations in the lung, including hypoxia/reoxygenation. This work seeks to clarify the current controversy concerning the double protective/toxic role of endogenous NO under hypoxia/reoxygenation situations in the lung by using a nitric oxide synthase (NOS) inhibitor, in a novel approach to address the problems raised from assaults under such circumstances. A follow-up study was conducted in Wistar rats submitted to hypoxia/reoxygenation (hypoxia for 30 min; reoxygenation of 0 h, 48 h, and 5 days), with or without prior treatment using the nonselective NOS inhibitor L-NAME (1.5 mM, in drinking water). Lipid peroxidation, apoptosis level, protein nitration, in situ NOS activity and NO production (NOx) were analyzed. This is the first work to focus on the time-course effects of L-NAME in the adult rat lung submitted to hypoxia/reoxygenation. The results showed that after L-NAME administration, in situ NOS activity was almost completely eliminated and consequently, NOx levels fell. Lipid peroxidation and the percentage of apoptotic cells rose at the earliest reoxygenation time (0 h), but decreased in the later period (48 h and 5 days). Also nitrated protein expression decreased at 48 h and 5 days posthypoxia. These results suggest that NOS-derived NO exerts two different effects on lung hypoxia/reoxygenation injury depending on the reoxygenation time: NO has a beneficial role just after the hypoxic stimulus and a deleterious effect in the later reoxygenation times. Moreover, we propose that this dual role of NO depends directly on the producer NOS isoform.