{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:21:29Z","timestamp":1768486889298,"version":"3.49.0"},"reference-count":54,"publisher":"American Physiological Society","issue":"3","funder":[{"name":"Griffith University Postgraduate Fellowship"},{"name":"Australian Commonwealth"}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:p> In vitro investigations demonstrate that human erythrocytes synthesize nitric oxide via a functional isoform of endothelial nitric oxide synthase (NOS) (RBC-NOS). We tested the hypothesis that phosphorylation of RBC-NOS at serine residue 1177 (RBC-NOS<jats:sup>1177<\/jats:sup>) would be amplified in blood draining-active skeletal muscle. Furthermore, given hypoxemia modulates local blood flow and thus shear stress, and nitric oxide availability, we performed duplicate experiments under normoxia and hypoxia. Nine healthy volunteers performed rhythmic handgrip exercise at 60% of individualized maximal workload for 3.5 min while breathing room air (normoxia) and after being titrated to an arterial oxygen saturation \u224880% (hypoxemia). We measured brachial artery blood flow by high-resolution duplex ultrasound, while continuously monitoring vascular conductance and mean arterial pressure using finger photoplethysmography. Blood was sampled during the final 30 s of each stage from an indwelling cannula. Blood viscosity was measured to facilitate calculation of accurate shear stresses. Erythrocytes were assessed for levels of phosphorylated RBC-NOS<jats:sup>1177<\/jats:sup> and cellular deformability from blood collected at rest and during exercise. Forearm exercise increased blood flow, vascular conductance, and vascular shear stress, which coincided with a 2.7 \u00b1 0.6-fold increase in RBC-NOS<jats:sup>1177<\/jats:sup> phosphorylation ( P &lt; 0.0001) and increased cellular deformability ( P &lt; 0.0001) under normoxia. When compared with normoxia, hypoxemia elevated vascular conductance and shear stress ( P &lt; 0.05) at rest, while cellular deformability ( P &lt; 0.01) and RBC-NOS<jats:sup>1177<\/jats:sup> phosphorylation ( P &lt; 0.01) increased. Hypoxemic exercise elicited further increases in vascular conductance, shear stress, and cell deformability ( P &lt; 0.0001), although a subject-specific response in RBC-NOS<jats:sup>1177<\/jats:sup> phosphorylation was observed. Our data yield novel insights into the manner that hemodynamic force and oxygen tension modulate RBC-NOS in vivo. <\/jats:p>","DOI":"10.1152\/ajpregu.00017.2023","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T08:00:15Z","timestamp":1688976015000},"page":"R260-R268","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of red blood cell nitric oxide synthase phosphorylation in the quiescent and exercising human forearm"],"prefix":"10.1152","volume":"325","author":[{"given":"Jeffrey A.","family":"Leo","sequence":"first","affiliation":[{"name":"Exercise and Sport, School of Health Sciences and Social Work, Griffith University, Gold Coast, Queensland, 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