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The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region‐specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L‐NMMA, administered in a randomized, single‐blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L‐NMMA (or volume‐matched saline) was infused intravenously for 5 min prior to imaging. L‐NMMA reduced CBF (L‐NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5–7%) in anterior and posterior cerebral circulations, due in part to the reduced cross‐sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L‐NMMA (L‐NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7–11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. Key points: Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear.Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously.Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L‐NMMA) reduced CBF by up to 11% in different brain regions.NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling. [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.

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]