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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.

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]

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]