Effect on rat arterial blood pressure of chemically generated peroxyl radicals and protection by antioxidants

Peluso, Ilaria; Serafini, Mauro; Campolongo, Patrizia; Palmery, Maura

doi:10.1016/j.jnutbio.2004.02.001

Cited by 8 publications

(2 citation statements)

References 23 publications

(26 reference statements)

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“…Depending on the chemical environment, these free radicals can play a causative role in oxidative stress and associated damage, or, conversely, contribute to vasodilation. For instance, peroxy-based radicals induced a dose-dependent decrease in blood pressure in healthy rodents that was abolished following antioxidant treatment [76], but have also been linked to lipid peroxidation, platelet aggregation, mitochondrial DNA damage, and endothelial dysfunction [77]. Furthermore, under physiological conditions, H 2 O 2 acts as a vasodilator [78] and regulator of eNOS levels during exercise training; however, under pathophysiological conditions with high oxidative stress, H 2 O 2 evokes a contractile or vasoconstrictor response in the vascular smooth muscle [79].…”

Section: Free Radical Regulation Of Vascular Functionmentioning

confidence: 99%

Regulation of exercise blood flow: Role of free radicals

Trinity

Broxterman

Richardson

2016

Free Radical Biology and Medicine

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During exercise, oxygen and nutrient rich blood must be delivered to the active skeletal muscle, heart, skin, and brain through the complex and highly regulated integration of central and peripheral hemodynamic factors. Indeed, even minor alterations in blood flow to these organs have profound consequences on exercise capacity by modifying the development of fatigue. Therefore, the fine-tuning of blood flow is critical for optimal physical performance. At the level of the peripheral circulation, blood flow is regulated by a balance between the mechanisms responsible for vasodilation and vasoconstriction. Once thought of as toxic by-products of in vivo chemistry, free radicals are now recognized as important signaling molecules that exert potent vasoactive responses that are dependent upon the underlying balance between oxidation-reduction reactions or redox balance. Under normal healthy conditions with low levels of oxidative stress, free radicals promote vasodilation, which is attenuated with exogenous antioxidant administration. Conversely, with advancing age and disease where background oxidative stress is elevated, an exercise-induced increase in free radicals can further shift the redox balance to a pro-oxidant state, impairing vasodilation and attenuating blood flow. Under these conditions, exogenous antioxidants improve vasodilatory capacity and augment blood flow by restoring an “optimal” redox balance. Interestingly, while the active skeletal muscle, heart, skin, and brain all have unique functions during exercise, the mechanisms by which free radicals contribute to the regulation of blood flow is remarkably preserved across each of these varied target organs.

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Section: Free Radical Regulation Of Vascular Functionmentioning

confidence: 99%

Regulation of exercise blood flow: Role of free radicals

Trinity

Broxterman

Richardson

2016

Free Radical Biology and Medicine

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“…The main aim of this study was to see whether the intravenous administration of L,D-DTT to unanesthetized rats would influence the ventilatory responses that occur during a HH gas challenge and upon return to room-air. L,D-DTT, which can interchange between reduced (free sulfurs) and oxidized (disulfide bond) forms (Figure 1), has been given to experimental animals to address the role of redox status in a variety of conditions and disease states [68][69][70][71][72][73][74][75]. To build on information gathered from the L,D-DTT study, we examined whether pretreatment with N-acetyl-Lcysteine methyl ester (L-NACme, Figure 1), which is a cell-penetrant L-thiolester reducing agent [76][77][78][79][80][81][82][83][84][85], was able to mimic the effects of L,D-DTT.…”

Section: Introductionmentioning

confidence: 99%

The Reducing Agent Dithiothreitol Modulates the Ventilatory Responses That Occur in Freely Moving Rats during and following a Hypoxic–Hypercapnic Challenge

Getsy,

Coffee,

May

et al. 2024

Antioxidants

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The present study examined the hypothesis that changes in the oxidation–reduction state of thiol residues in functional proteins play a major role in the expression of the ventilatory responses in conscious rats that occur during a hypoxic–hypercapnic (HH) gas challenge and upon return to room air. A HH gas challenge in vehicle-treated rats elicited robust and sustained increases in minute volume (via increases in frequency of breathing and tidal volume), peak inspiratory and expiratory flows, and inspiratory and expiratory drives while minimally affecting the non-eupneic breathing index (NEBI). The HH-induced increases in these parameters, except for frequency of breathing, were substantially diminished in rats pre-treated with the potent and lipophilic disulfide-reducing agent, L,D-dithiothreitol (100 µmol/kg, IV). The ventilatory responses that occurred upon return to room air were also substantially different in dithiothreitol-treated rats. In contrast, pre-treatment with a substantially higher dose (500 µmol/kg, IV) of the lipophilic congener of the monosulfide, N-acetyl-L-cysteine methyl ester (L-NACme), only minimally affected the expression of the above-mentioned ventilatory responses that occurred during the HH gas challenge or upon return to room air. The effectiveness of dithiothreitol suggests that the oxidation of thiol residues occurs during exposure to a HH gas challenge and that this process plays an essential role in allowing for the expression of the post-HH excitatory phase in breathing. However, this interpretation is contradicted by the lack of effects of L-NACme. This apparent conundrum may be explained by the disulfide structure affording unique functional properties to dithiothreitol in comparison to monosulfides. More specifically, the disulfide structure may give dithiothreitol the ability to alter the conformational state of functional proteins while transferring electrons. It is also possible that dithiothreitol is simply a more efficient reducing agent following systemic injection, although one interpretation of the data is that the effects of dithiothreitol are not due to its reducing ability.

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