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Oral phosphodiesterase-5 inhibitor does not augment red blood cell deformability at rest or during handgrip exercise

Steele AR, Kightley-Kauser LA, McCormick J, Geerts NK, Lemkes B, Dizon JC, Carr JMJR, Ainslie PN

European journal of applied physiology, 2026

4 citations

Abstract

PURPOSE: Red blood cells (RBCs) rely on deformability for oxygen delivery and capillary transit. Sildenafil citrate, a phosphodiesterase-5 inhibitor (PDE5-i), may enhance RBC deformability via nitric oxide, yet in vivo effects remain unclear. METHODS: We conducted a double-blind, placebo-controlled study to assess the effects of PDE5-i on cerebral blood flow (CBF), brachial artery (BA) blood flow (Q) and shear stress-specific RBC deformability during handgrip exercise (Baseline [BL], 27.5% and 55% of maximal voluntary contraction [MVC]). Fourteen participants (8F; age: 24 ± 6) were tested on separate days, before and 60-min following ingestion of sildenafil citrate (100 mg) or placebo. CBF and BA Q were measured using duplex ultrasound and RBC deformability was assessed with a laser-assisted optical rotational red cell analyzer. RESULTS: Acute oral administration of PDE5-i had no effect on basal cerebral or BA vascular metrics, including diameter, shear stress, Q, BA shear stress-specific RBC deformability or exercise hyperemia (p > 0.05). Prior to PDE5-i administration, exercise increased RBC deformability [EImax] (BL: 0.55 ± 0.021; 27.5% MVC: 0.57 ± 0.014; 55% MVC: 0.58 ± 0.015 a.u. p 0.05), a pattern not observed with placebo. EImax did not differ between PDE5-i and placebo at matched exercise intensities post-administration (p > 0.05), indicating no independent effect of PDE5-i on RBC deformability. CONCLUSION: Acute PDE5-i administration does not independently alter RBC…

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