New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans.

KEY POINTS: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2 -[H+ ] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2 -[H+ ] washout. ABSTRACT: The hypothetical mechanism for the increase in ventilation ( V̇E ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2 -[H+ ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in V̇E , 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. V̇E , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2 ) and CO2 (PCO2 ), pH, oxidant (8-isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8-isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8-isoprostane and attenuated both the reduction in CBF and the HX-induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans-cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2 , which, in turn, seems to be evoked by the excessive ROS production/accumulation.

Fluctuations in cardiac stroke volume during rowing.

Preload to the heart may be limited during rowing because both blood pressure and central venous pressure increase when force is applied to the oar. Considering that only the recovery phase of the rowing stroke allows for unhindered venous return, rowing may induce large fluctuations in stroke volume (SV). Thus, the purpose of this study was to evaluate SV continuously during the rowing stroke. Eight nationally competitive oarsmen (mean ± standard deviation: age 21 ± 2 years, height 190 ± 9 cm, and weight 90 ± 10 kg) rowed on an ergometer at a targeted heart rate of 130 and 160 beats per minute. SV was derived from arterial pressure waveform by pulse contour analysis, while ventilation and force on the handle were measured. Mean arterial pressure was elevated during the stroke at both work rates (to 133 ± 10 [P < .001] and 145 ± 11 mm Hg [P = .024], respectively). Also, SV fluctuated markedly during the stroke with deviations being largest at the higher work rate. Thus, SV decreased by 27 ± 10% (31 ± 11 mL) at the beginning of the stroke and increased by 25 ± 9% (28 ± 10 mL) in the recovery (P = .013), while breathing was entrained with one breath during the drive of the stroke and one prior to the next stroke. These observations indicate that during rowing cardiac output depends critically on SV surges during the recovery phase of the stroke.

Hypertension impairs hypoxia-induced angiogenesis in men.

OBJECTIVE: The inability of the organism to appropriately respond to hypoxia results in abnormal cell metabolism and function. Hypoxia-induced angiogenesis seems to be suppressed in experimental models of hypertension; however, this hypothesis has not been tested in humans. We examined changes in endothelial biomarkers and vascular chemoattraction/angiogenic capacity in response to isocapnic hypoxia in hypertensive men. METHODS: Twelve normotensive (38 ±â€Š10 years) and nine hypertensive men (45 ±â€Š11 years) were exposed to 5-min trials of normoxia (21% O2) and isocapnic hypoxia (10% O2). During the last minute of each trial, venous blood was drawn. Endothelial progenitor cells (EPCs; CD45/CD34/VEGFR2), endothelial microvesicles (apoptotic EMVs, CD42b/CD31/AnnexinV; endothelial activation, CD62E/CD144), nitrite, vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1) were measured. RESULTS: During normoxia, EPCs, nitrite, endothelial activation, and SDF-1 were similar between groups, whereas VEGF was lower (P = 0.02) and apoptotic EMVs tended to increase (P = 0.07) in hypertensive men. During isocapnic hypoxia, endothelial activation increased in both groups (normotensive, P = 0.007 vs. normoxia; hypertensive, P = 0.006 vs. normoxia), whereas EMVs were higher only in the hypertensive group (P = 0.03 vs. normotensive). EPCs (P = 0.01 vs. normoxia; P = 0.03 vs. hypertensive men), NO (P = 0.01 vs. normoxia; P = 0.04 vs. hypertensive), and VEGF (P = 0.02 vs. normoxia; P = 0.0005 vs. hypertensive) increased only in normotensive individuals in response to isocapnic hypoxia. SDF-1 did not change in either group. CONCLUSION: These results suggest that hypertension-induced impairment in angiogenesis in response to isocapnic hypoxia is related to disrupted NO bioavailability, VEGF chemotactic signaling, and EPC mobilization.

KATP channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans.

KEY POINTS: ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia. Hypoxia-induced increases in the anterior circulation and total cerebral perfusion were attenuated under KATP channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, KATP channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO2 responses to hypoxia. ABSTRACT: ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia in humans. Nine healthy men were exposed to 5-min trials of normoxia and isocapnic hypoxia (IHX, 10% O2 ) before (BGB) and 3 h after glibenclamide ingestion (AGB). Mean arterial pressure (MAP), arterial saturation ( SaO2 ), partial pressure of oxygen ( PaO2 ) and carbon dioxide ( PaCO2 ), internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF), total (t)CBF (Doppler ultrasound) and CDO2 were quantified during the trials. IHX provoked similar reductions in SaO2 and PaO2 , while MAP was not affected by oxygen desaturation or KATP blockade. A smaller increase in ICABF (ΔBGB: 36 ± 23 vs. ΔAGB 11 ± 18%, p = 0.019) but not in VABF (∆BGB 26 ± 21 vs. ∆AGB 27 ± 27%, p = 0.893) was observed during the hypoxic trial under KATP channels blockade. Thus, IHX-induced increases in tCBF (∆BGB 32 ± 19 vs. ∆AGB 14 ± 13%, p = 0.012) and CDO2 relative changes (∆BGB 7 ± 13 vs. ∆AGB -6 ± 14%, p = 0.048) were attenuated during the AGB hypoxic trial. In a separate protocol, 6 healthy men (5 from protocol 1) underwent a 5-min exposure to normoxia and IHX before and 3 h after placebo (5 mg of cornstarch) ingestion. IHX reduced SaO2 and PaO2 , but placebo did not affect the ICABF, VABF, tCBF, or CDO2 responses. Therefore, in humans, KATP channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO2 responses to hypoxia.

Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation.

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

Acid-sensing ion channels blockade attenuates pressor and sympathetic responses to skeletal muscle metaboreflex activation in humans.

In animals, the blockade of acid-sensing ion channels (ASICs), cation pore-forming membrane proteins located in the free nerve endings of group IV afferent fibers, attenuates increases in arterial pressure (AP) and sympathetic nerve activity (SNA) during muscle contraction. Therefore, ASICs play a role in mediating the metabolic component (skeletal muscle metaboreflex) of the exercise pressor reflex in animal models. Here we tested the hypothesis that ASICs also play a role in evoking the skeletal muscle metaboreflex in humans, quantifying beat-by-beat mean AP (MAP; finger photoplethysmography) and muscle SNA (MSNA; microneurography) in 11 men at rest and during static handgrip exercise (SHG; 35% of the maximal voluntary contraction) and postexercise muscle ischemia (PEMI) before (B) and after (A) local venous infusion of either saline or amiloride (AM), an ASIC antagonist, via the Bier block technique. MAP (BAM +30 ± 6 vs. AAM +25 ± 7 mmHg, P = 0.001) and MSNA (BAM +14 ± 9 vs. AAM +10 ± 6 bursts/min, P = 0.004) responses to SHG were attenuated under ASIC blockade. Amiloride also attenuated the PEMI-induced increases in MAP (BAM +25 ± 6 vs. AAM +16 ± 6 mmHg, P = 0.0001) and MSNA (BAM +16 ± 9 vs. AAM +8 ± 8 bursts/min, P = 0.0001). MAP and MSNA responses to SHG and PEMI were similar before and after saline infusion. We conclude that ASICs play a role in evoking pressor and sympathetic responses to SHG and the isolated activation of the skeletal muscle metaboreflex in humans. NEW & NOTEWORTHY We showed that regional blockade of the acid-sensing ion channels (ASICs), induced by venous infusion of the antagonist amiloride via the Bier block anesthetic technique, attenuated increases in arterial pressure and muscle sympathetic nerve activity during both static handgrip exercise and postexercise muscle ischemia. These findings indicate that ASICs contribute to both pressor and sympathetic responses to the activation of the skeletal muscle metaboreflex in humans.

Human brain blood flow and metabolism during isocapnic hyperoxia: the role of reactive oxygen species.

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 (CMR O2 ) 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 CMRO2 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, CMRO2 , 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 (CMR O2 ), 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 CMRO2 , 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 CMRO2 . These findings indicate that ROS play a role in CBF regulation and metabolism during IH without evidence of BBB disruption or neural-parenchymal damage.

Muscle sympathetic nerve activity and hemodynamic responses to venous distension: does sex play a role?

Peripheral venous distension mechanically stimulates type III/IV sensory fibers in veins and evokes pressor and sympathoexcitatory reflex responses in humans. As young women have reduced venous compliance and impaired sympathetic transduction, we tested the hypothesis that pressor and sympathoexcitatory responses to venous distension may be attenuated in women compared with men. Mean arterial pressure (photoplethysmography), heart rate (HR), stroke volume (SV; Modelflow), cardiac output (CO = HR × SV), muscle sympathetic nerve activity (MSNA), femoral artery blood flow, and femoral artery conductance (Doppler ultrasound) were quantified in eight men (27 ± 4 yr) and nine women (28 ± 4 yr) before [control (CON)], during (INF), and immediately after (post-INF) a local infusion of saline [5% of the total forearm volume (30 ml/min); the infusion time was 2 ± 1 and 1 ± 1 min ( P = 0.0001) for men and women, respectively] through a retrograde catheter inserted into an antecubital vein, to which venous drainage and arterial supply had been occluded. Mean arterial pressure increased during and after infusion in both groups (vs. the CON group, P < 0.05), but women showed a smaller pressor response in the post-INF period (Δ+7.2 ± 2.0 vs. Δ+18.3 ± 3.9 mmHg in men, P = 0.019). MSNA increased and femoral artery conductance decreased similarly in both groups (vs. the CON group, P < 0.05) at post-INF. Although 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 compared with women. Therefore, venous distension evokes a smaller pressor response in young women due to attenuated cardiac adjustments rather than reduced venous compliance or sympathetic transduction. NEW & NOTEWORTHY We found that the pressor response to venous distension was attenuated in young women compared with age-matched men. This was due to attenuated cardiac adjustments rather than reduced venous compliance, sympathetic activation, or impaired transduction and vascular control. Collectively, these findings suggest that an attenuated venous distension reflex could be involved in orthostatic intolerance in young women.

Disturbed blood flow induces endothelial apoptosis without mobilizing repair mechanisms in hypertension.

AIMS: The influence of blood flow disturbances on vascular function, endothelial activation and repair capacity has not been fully elucidated either in physiological conditions or in cardiovascular disease. We aimed to determine the impact of increases in retrograde blood flow (RBF) on vascular function, endothelial biomarkers and repair capacity in healthy subjects and patients with hypertension. MAIN METHODS: In seven healthy (CT; 32 ±â€¯15 yr) and eight hypertensive (HT; 34 ±â€¯23 yr) men, flow mediated-dilation (FMD) was assessed before and 10 min after a 30-min maneuver to increase brachial artery RBF in which a pneumatic cuff was inflated to 75 mm Hg on forearm. Blood samples were obtained at rest and during the last minute of the maneuver. KEY FINDINGS: Endothelial activation, apoptosis and endothelial progenitor cells (EPC) were measured by flow cytometry; nitrite was measured by ozone-chemiluminescence. No significant disparities were observed in FMD, endothelial activation and circulating EPC between groups at baseline (p > 0.05). However, HT presented higher resting endothelial apoptosis (p = 0.01 vs CT). Exacerbated RBF induced reductions in FMD (p = 0.02 vs baseline) and increases in endothelial activation in both groups (p = 0.049 vs baseline). Endothelial apoptosis increased only in HT (p = 0.02 vs baseline; p = 0.004 vs CT), whereas EPC (p = 0.02 vs baseline; p = 0.03 vs HT) and nitrite (p = 0.04 vs baseline; p = 0.004 vs HT) increased only in CT during the maneuver. SIGNIFICANCE: While findings indicate that increased RBF impairs endothelial function and triggers the EPC mobilization in healthy subjects, patients with hypertension presented greater apoptosis and impaired repair capacity in response to RBF.

Reduced arterial vasodilatation in response to hypoxia impairs cerebral and peripheral oxygen delivery in hypertensive men.

KEY POINTS: Hypoxaemia evokes a repertoire of homeostatic adjustments that maintain oxygen supply to organs and tissues including the brain and skeletal muscles. Because hypertensive patients have impaired endothelial-dependent vasodilatation and an increased sympathetic response to arterial oxygen desaturation, we investigated whether hypertension impairs isocapnic hypoxia-induced cerebral and skeletal muscle hyperaemia to an extent that limits oxygen supply. In middle-aged hypertensive men, vertebral and femoral artery blood flow do not increase in response to isocapnic hypoxia, limiting brain and peripheral hyperaemia and oxygen supply. Increased chemoreflex-induced sympathetic activation impairs skeletal muscle perfusion and oxygen supply, whereas an attenuation of local vasodilatory signalling in the posterior cerebrovasculature reduced brain hyperperfusion of hypertensive middle-aged men in response to isocapnic hypoxia. ABSTRACT: 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% O2 ) and IH (10% O2 ). Total cerebral blood flow (tCBF), brain (CDO2 ) and leg (LDO2 ) 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. CDO2 only increased in NT and LDO2 decreased in HT. Furthermore, IH evoked a greater increase in HT MSNA. Changes in MSNA were inversely related to FA BF, LDO2 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.

Selective α1-adrenergic blockade disturbs the regional distribution of cerebral blood flow during static handgrip exercise.

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.

Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate.

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.