Nitric oxide (NO) inhibits platelet function and plays a key role in the regulation of cardiovascular homeostasis. Essential hypertension is characterized by an increased risk of thrombus formation, and by an inhibition of intraplatelet NO bioactivity. We have previously shown that membrane transport of L-arginine is a rate-limiting step for plateletderived NO synthesis. This study examined the effects of exercise on the platelet L-arginine-NO pathway and aggregation and systemic inflammation markers in 13 sedentary hypertensive patients subjected to 60 min of training activity (exercise group), predominantly aerobic, three times a week for a period of 12 weeks. Six sedentary hypertensive patients participated in the control group.After 12 weeks, L-arginine transport was significantly increased and associated with increased platelet NO synthase activity and cGMP levels and reduced platelet aggregation. Moreover, exercise training reduced plasma concentrations of fibrinogen and C-reactive protein and blood pressure. The control group did not change their previous intraplatelet L-arginine-NO results and systemic inflammatory markers levels. Thus, exercise training reduces inflammatory responses, restores NO synthesis in platelets and thereby contributes to the beneficial effects of exercise in hypertension. The present study adds exercise as a new tool to reduce morbidity and mortality associated with platelet activation in hypertension.
1. An increase in plasma concentrations of endogenous L-arginine analogues, which are inhibitors of nitric oxide (NO) synthesis, may be involved in platelet activation and the increased risk of thrombosis in essential hypertension. Nitric oxide is synthesised in platelets from the amino acid L-arginine by inducible and constitutive isoforms of NO synthase (NOS), which leads to increased levels of cGMP. 2. In the present study, we investigated basal intraplatelet cGMP levels, platelet aggregation and pro-inflammatory biomarkers in hypertensive patients. The effects of endogenous (N(G)-monomethyl-L-arginine (L-NMMA) and asymmetric dimethylarginine (ADMA); both at 1 mmol/L) and exogenous (aminoguanidine and N(G)-nitro-L-arginine; both at 1 mmol/L) L-arginine analogues and the neutral amino acid L-leucine (1 mmol/L) in inhibiting NOS activity in platelets were also investigated. 3. Twelve healthy controls and 18 hypertensive patients participated in the study. Platelet aggregation induced by collagen was increased in hypertensive patients (95 +/- 5%) compared with controls (72 +/- 5%). Basal NOS activity and intraplatelet cGMP levels were reduced in hypertensive platelets. Moreover, ADMA, L-NMMA and L-leucine were effective inhibitors of NO synthesis in both hypertensive and control platelets. Essential hypertension led to an inflammatory response, with increased plasma concentrations of fibrinogen, C-reactive protein and cytokines. 4. These findings provide evidence that, in essential arterial hypertension, the enhanced plasma levels of endogenous L-arginine analogues ADMA and L-NMMA, potent inhibitors of L-arginine transport and NO synthesis in platelets, may play a role in increased platelet aggregation via a cGMP-dependent mechanism.
Selenium (Se) is an essential micronutrient with a narrow essentiality-toxicity range known to bioaccumulate in aquatic food webs. Selenium uptake and trophic transfer at the base of aquatic food chains represent a great source of uncertainty for Se risk assessment. The goal of the present study was to investigate Se distribution in water and sediment and its subsequent transfer into the periphyton-benthic macroinvertebrate (BMI) food chain in boreal lakes downstream from a Saskatchewan uranium mill. In particular, the present study aimed to assess potential differences in Se bioaccumulation patterns by BMI taxa to contribute to the current knowledge gap. During summer 2018 and 2019, water, sediment, periphyton, and BMI were sampled at two sites in Vulture Lake, seven sites in McClean Lake east basin, and one reference site in McClean Lake west basin. Periphyton and BMI taxa were sampled with artificial substrates (Hester-Dendy) deployed for 5 weeks in 2018 and 7 weeks in 2019; BMI were sorted into the lowest practical achievable taxonomic level and analyzed for total Se concentrations. At the diluted effluent exposure sites, Se concentrations in BMI ranged from 1.3 to 18.0 µg/g dry weight and from 0.3 to 49.3 µg/g dry weight in 2018 and 2019, respectively, whereas concentrations ranged from 0.01 to 3.5 µg/g dry weight at the reference site. Selenium concentrations in periphyton and some BMI taxa sampled near the effluent diffuser (Se < 1 µg/L) reached levels comparable to higher effluent exposure sites (Se > 2 µg/L). Despite differences in Se bioaccumulation among BMI taxa, an approximately one-to-one trophic transfer ratio was observed for benthic primary consumers and benthic predatory taxa.
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