Key points It is unknown whether excessive reactive oxygen species (ROS) production drives the isocapnic hyperoxia (IH)‐induced decline in human cerebral blood flow (CBF) via reduced nitric oxide (NO) bioavailability and leads to disruption of the blood–brain barrier (BBB) or neural‐parenchymal damage. Cerebral metabolic rate for oxygen (CMRnormalO2) and transcerebral exchanges of NO end‐products, oxidants, antioxidants and neural‐parenchymal damage markers were simultaneously quantified under IH with intravenous saline and ascorbic acid infusion. CBF and CMR normalO2 were reduced during IH, responses that were followed by increased oxidative stress and reduced NO bioavailability when saline was infused. No indication of neural‐parenchymal damage or disruption of the BBB was observed during IH. Antioxidant defences were increased during ascorbic acid infusion, while CBF, CMR normalO2, oxidant and NO bioavailability markers remained unchanged. ROS play a role in the regulation of CBF and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage. Abstract To test the hypothesis that isocapnic hyperoxia (IH) affects cerebral blood flow (CBF) and metabolism through exaggerated reactive oxygen species (ROS) production, reduced nitric oxide (NO) bioavailability, disturbances in the blood–brain barrier (BBB) and neural‐parenchymal homeostasis, 10 men (24 ± 1 years) were exposed to a 10 min IH trial (100% O2) while receiving intravenous saline and ascorbic acid (AA, 3 g) infusion. Internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF) and total CBF (tCBF, Doppler ultrasound) were determined. Arterial and right internal jugular venous blood was sampled to quantify the cerebral metabolic rate of oxygen (CMRnormalO2), transcerebral exchanges (TCE) of NO end‐products (plasma nitrite), antioxidants (AA and AA plus dehydroascorbic acid (AA+DA)) and oxidant biomarkers (thiobarbituric acid‐reactive substances (TBARS) and 8‐isoprostane), and an index of BBB disruption and neuronal‐parenchymal damage (neuron‐specific enolase; NSE). IH reduced ICABF, tCBF and CMR normalO2, while VABF remained unchanged. Arterial 8‐isoprostane and nitrite TCE increased, indicating that CBF decline was related to ROS production and reduced NO bioavailability. AA, AA+DA and NSE TCE did not change during IH. AA infusion did not change the resting haemodynamic and metabolic parameters but raised antioxidant defences, as indicated by increased AA/AA+DA concentrations. Negative AA+DA TCE, unchanged nitrite, reductions in arterial and venous 8‐isoprostane, and TBARS TCE indicated that AA infusion effectively inhibited ROS production and preserved NO bioavailability. Similarly, AA infusion prevented IH‐induced decline in regional and total CBF and re‐established CMR normalO2. These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural‐parenchymal damage.

The present study investigated whether hypertension impairs isocapnic hypoxia (IH)-induced cerebral and skeletal muscle hyperaemia to an extent that limits oxygen supply. Oxygen saturation (oxymetry), mean arterial pressure (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneugraphy), as well as femoral artery (FA), internal carotid artery and vertebral artery (VA) blood flow (BF; Doppler ultrasound), were quantified in nine normotensive (NT) (aged 40 ± 11 years, systolic pressure 119 ± 7 mmHg and diastolic pressure 73 ± 6 mmHg) and nine hypertensive men (HT) (aged 44 ± 12 years, systolic pressure 152 ± 11 mmHg and diastolic pressure 90 ± 9 mmHg) during 5 min of normoxia (21% O ) and IH (10% O ). Total cerebral blood flow (tCBF), brain (CDO ) and leg (LDO ) oxygen delivery were estimated. IH provoked similar oxygen desaturation without changing mean arterial pressure. Internal carotid artery perfusion increased in both groups during IH. However, VA and FA BF only increased in NT. Thus, IH-induced increase in tCBF was smaller in HT. CDO only increased in NT and LDO decreased in HT. Furthermore, IH evoked a greater increase in HT MSNA. Changes in MSNA were inversely related to FA BF, LDO and end-tidal oxygen tension. In conclusion, hypertension disturbs regional and total cerebrovascular and peripheral responses to IH and consequently limits oxygen supply to the brain and skeletal muscle. Although increased chemoreflex-induced sympathetic activation may explain impaired peripheral perfusion, attenuated vasodilatory signalling in the posterior cerebrovasculature appears to be responsible for the small increase in tCBF when HT were exposed to IH.

Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P < 0.05 vs. baseline), whereas exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P < 0.05 vs. baseline). In conclusion, exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

Peripheral venous distension mechanically stimulates type III/IV sensory fibers in veins and evokes pressor and sympathoexcitatory reflex responses in humans. As young females have reduced venous compliance, smaller increases in arterial pressure to type III/IV sensory fibers activation and impaired sympathetic transduction, we tested the hypothesis that pressor and sympathoexcitatory responses to venous distension may be attenuated in women compared to men. Mean arterial pressure (MAP, photoplethysmography), heart rate (HR), stroke volume (SV, Modelflow), cardiac output (CO = HR x SV), muscle sympathetic nerve activity (MSNA), femoral artery blood flow and conductance (FABF and FACT, Doppler ultrasound) were quantified in 8 males (27 ± 4 yrs.) and 9 females (28 ± 4 yrs.) before (CON) during (INF) and after (Post‐INF) a local infusion of normal saline (5% of the forearm volume) through a retrograde catheter inserted into an antecubital vein of the forearm, to which venous drainage and arterial supply had been occluded. MAP increased during and after infusion in both groups (vs. CON, p ≤ 0.05) but women showed a smaller pressor response in the Post‐INF period (Δ+7.2 ± 2.0 vs. men Δ+18.3 ± 3.9 mmHg, p = 0.019). MSNA increased and FACT decreased similarly in both groups (vs. CON, p ≤ 0.05) at Post‐INF. While HR changes were similar, increases in SV (Δ+20.4 ± 8.6 vs. Δ+2.6 ± 2.7 mL, p = 0.05) and CO (Δ+0.84 ± 0.17 vs. Δ+0.34 ± 0.10 L/min, p = 0.024) were greater in men than women. Therefore, these findings indicate that venous distension evokes a smaller pressor response in young women due to attenuated cardiac adjustments rather than to reduced venous compliance or sympathetic transduction. Support or Funding Information Support: CNPq, CAPES, FAPERJ This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Handgrip-induced increases in blood flow through the contralateral artery that supplies the cortical representation of the arm have been hypothesized as a consequence of neurovascular coupling and a resultant metabolic attenuation of sympathetic cerebral vasoconstriction. In contrast, sympathetic restraint, in theory, inhibits changes in perfusion of the cerebral ipsilateral blood vessels. To confirm whether sympathetic nerve activity modulates cerebral blood flow distribution during static handgrip (SHG) exercise, beat-to-beat contra- and ipsilateral internal carotid artery blood flow (ICA; Doppler) and mean arterial pressure (MAP; Finometer) were simultaneously assessed in nine healthy men (27 ± 5 yr), both at rest and during a 2-min SHG bout (30% maximal voluntary contraction), under two experimental conditions: 1) control and 2) α1-adrenergic receptor blockade. End-tidal carbon dioxide (rebreathing system) was clamped throughout the study. SHG induced increases in MAP (+31.4 ± 10.7 mmHg, P < 0.05) and contralateral ICA blood flow (+80.9 ± 62.5 ml/min, P < 0.05), while no changes were observed in the ipsilateral vessel (-9.8 ± 39.3 ml/min, P > 0.05). The reduction in ipsilateral ICA vascular conductance (VC) was greater compared with contralateral ICA (contralateral: -0.8 ± 0.8 vs. ipsilateral: -2.6 ± 1.3 ml·min(-1)·mmHg(-1), P < 0.05). Prazosin was effective to induce α1-blockade since phenylephrine-induced increases in MAP were greatly reduced (P < 0.05). Under α1-adrenergic receptor blockade, SHG evoked smaller MAP responses (+19.4 ± 9.2, P < 0.05) but similar increases in ICAs blood flow (contralateral: +58.4 ± 21.5 vs. ipsilateral: +54.3 ± 46.2 ml/min, P > 0.05) and decreases in VC (contralateral: -0.4 ± 0.7 vs. ipsilateral: -0.4 ± 1.0 ml·min(-1)·mmHg(-1), P > 0.05). These findings indicate a role of sympathetic nerve activity in the regulation of cerebral blood flow distribution during SHG.