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Central adiposity is associated with greater sympathetic support of blood pressure. b-adrenergic receptors (b-AR) buffer sympathetically mediated vasoconstriction and b-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized b-AR vasodilation would be lower in obese compared with normal weight adults. Because b-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to b-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (DFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [NG-monomethyl-L-arginine (L-NMMA)], COX (ketorolac), and NOS þ COX (L-NMMA þ ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). L-NMMA attenuated Iso-mediated DFVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased Iso-mediated DFVC (P < 0.01) and this response was lost with concurrent L-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac þ L-NMMA (P = 0.40) altered Iso-mediated DFVC in adults with obesity. Despite shifts in COX and NOS, b-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity. [ABSTRACT FROM AUTHOR]

Near-infrared diffuse correlation spectroscopy (DCS) is a rapidly evolving optical imaging technique for the assessment of skeletal muscle O2 utilization (mVO2). We compared DCS-derived determinants of mVO2 with conventional measures [blood flow by brachial artery Doppler ultrasound and venous O2 saturation (SVO2 )] in eight volunteers at rest and during incremental handgrip exercise. Brachial artery blood flow and DCS-derived blood flow index (BFI) were linearly related (R2 = 0.57) and increased with each workload, whereas SVO2 decreased from 65.3 ± 2.5% (rest) to 39.9 ± 3.0% (light exercise; P < 0.01) with no change thereafter. In contrast, DCS-derived tissue O2 saturation decreased progressively with each incremental stage (P < 0.01), driven almost entirely by an initial steep rise in deoxyhemoglobin/myoglobin, followed by a linear increase thereafter. Whereas seemingly disparate at first glance, we believe these two approaches provide similar information. Indeed, by plotting the mean convective O2 delivery and diffusive O2 conductance, we show that the initial increase in mVO2 during the transition from rest to exercise was achieved by a greater increase in diffusive O2 conductance versus convective O2 delivery (10-fold vs. 4-fold increase, respectively), explaining the initial decline in SVO2 . In contrast, the increase in mVO2 from light to heavy exercise was achieved by equal increases (1.8-fold) in convective O2 delivery and diffusive O2 conductance, explaining the plateau in SVO2 . That DCS-derived BFI and deoxyhemoglobin/myoglobin (surrogate measure of O2 extraction) share the same general biphasic pattern suggests that both DCS and conventional approaches provide complementary information regarding the determinants of mVO2. NEW & NOTEWORTHY Near-infrared diffuse correlation spectroscopy (DCS) is an emerging optical imaging technique for quantifying skeletal muscle O2 delivery and utilization at the microvascular level. Here, we show that DCS provides complementary insight into the determinants of muscle O2 consumption across a wide range of exercise intensities, further establishing the utility of DCS. [ABSTRACT FROM AUTHOR]

Key points: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion.Near‐infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation.Here we compared a combined NIRS–DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS‐derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level.We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption.Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Combining DCS with near‐infrared spectroscopy (NIRS) introduces exciting possibilities for understanding the determinants of muscle oxygen consumption; however, no investigation has directly compared NIRS–DCS to conventional measures of oxygen delivery and utilization in an exercising limb. To address this knowledge gap, nine healthy males performed rhythmic handgrip exercise with simultaneous measurements by NIRS–DCS, Doppler blood flow and venous oxygen content. The two approaches showed good concurrent validity, with directionally similar responses between: (a) Doppler‐derived forearm blood flow and DCS‐derived blood flow index (BFI), and (b) venous oxygen saturation and NIRS‐derived tissue saturation. To explore the utility of combined NIRS–DCS across the physiological spectrum, we manipulated forearm arterial perfusion pressure by altering the arm position above or below the level of the heart. As expected, Doppler‐derived skeletal muscle blood flow increased with exercise in both arm positions, but with markedly different magnitudes (below: +424.3 ± 41.4 ml/min, above: +306 ± 12.0 ml/min, P = 0.002). In contrast, DCS‐derived microvascular BFI increased to a similar extent with exercise, regardless of arm position (P = 0.65). Importantly, however, the time to reach BFI steady state was markedly slower with the arm above the heart, supporting the experimental design. Notably, we observed faster tissue desaturation at the onset of exercise with the arm above the heart, resulting in similar muscle oxygen consumption profiles throughout exercise. Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of skeletal muscle oxygen utilization non‐invasively and throughout exercise. Key points: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion.Near‐infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation.Here we compared a combined NIRS–DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS‐derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level.We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption.Taken together, these data support a novel role for NIRS–DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [NGmonomethyl- L-arginine (L-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P < 0.01), and this effect was not different between men and women (P = 0.41). L-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P > 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol- mediated responses in both men (P < 0.01) and women (P = 0.04) and this rise was lost with subsequent L-NMMA infusion (men, P < 0.01; women, P < 0.05). β-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease. [ABSTRACT FROM AUTHOR]

Blunting of sympathetic vasoconstriction in exercising muscle is well-established. Whether it persists during the early post-exercise period is unknown. This study tested the hypothesis that it persists in human skeletal muscle during the first 10min of recovery from exercise. Eight healthy young males (21.4 ± 0.8 yrs, SE) performed 7min of forearm rhythmic isometric handgrip exercise at 15% below forearm critical force (fCF). In separate trials, a cold pressor test (CPT) of 2min duration was used to evoke forearm sympathetic vasoconstriction in each of Rest (R), Steady State Exercise (Ex), 2-4 min Post-Exercise (PEearly), and 8-10min Post-Exercise (PElate). A 7min control exercise trial with no CPT was also performed. Exercising forearm brachial artery blood flow, arterial blood pressure, cardiac output (CO), heart rate (HR), forearm deep venous catecholamine concentration, and arterialized venous catecholamine concentration were obtained immediately prior to and following the CPT in each trial. CPT resulted in a significant increase in forearm venous plasma norepinephrine concentration in all trials (P = 0.007), but no change in arterialized plasma norepinephrine (P = 0.32). CPT did not change forearm venous plasma epinephrine (P = 0.596) or arterialized plasma epinephrine concentration (P = 0.15). As assessed by the %reduction in forearm vascular conductance (FVC) the CPT evoked a robust vasoconstriction at rest that was severely blunted in exercise (R = -39.9 ± 4.6% vs. Ex = 5.5 ± 7.4%, P < 0.001). This blunting of vasoconstriction persisted at PEearly (-12.3 ± 10.1%, P = 0.02) and PElate (-18.1 ± 8.2%, P = 0.03) post-exercise. In conclusion, functional sympatholysis remains evident in human skeletal muscle as much as 10min after the end of a bout of forearm exercise. Persistence of functional sympatholysis may have important implications for blood pressure regulation in the face of a challenge to blood pressure following exercise. [ABSTRACT FROM AUTHOR]

The authors discuss research published within the issue concerning stiffness and blood flow problems in downstream and upstream arteries. Topics covered include the effects of the stiffness of large artery on cerebral and skeletal muscle vasculature, greater pulsability of the middle cerebral artery (MCA) compared to the gastrocnemius feed artery and the dependence of MCA on nitrous oxide to elicit dilatation.