Key result
NOS inhibition decelerated exercise-onset vasodilator kinetics (P=0.01), but concurrent PDE-5 inhibition with sildenafil restored kinetics to control levels (P=0.76).
Why the study?
Does sildenafil and/or l-NMMA alter vasodilation onset kinetics during forearm exercise in healthy adults?
Does sildenafil and/or l-NMMA alter vasodilation onset kinetics during forearm exercise in healthy adults?
p-value: p=0.90 for SDF, 0.01 for l-NMMA, 0.76 for SDF+l-NMMA
PDE-5 inhibition can restore exercise-mediated vasodilation onset kinetics via NO-independent cGMP pathways when NO bioavailability is reduced.
Nitric oxide (NO)-mediated vasodilation contributes to the rapid rise in muscle blood flow at exercise onset. This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Whether PDE-5 limits exercise vasodilation onset kinetics is unknown. We hypothesized the time course of exercise vasodilation would be 1) accelerated during PDE-5 inhibition (sildenafil citrate, SDF) and 2) decelerated during NO synthase inhibition ( N G -monomethyl-l-arginine, l-NMMA), and 3) the effect of SDF on vasodilation onset kinetics would be attenuated with concurrent l-NMMA. Data from 29 healthy adults were analyzed. Individuals completed 5 min of moderate-intensity forearm exercise under control conditions and during 1) oral SDF ( n = 8), 2) intra-arterial l-NMMA ( n = 15), or 3) combined SDF + l-NMMA ( n = 6). Forearm blood flow (FBF; Doppler ultrasound of the brachial artery) and mean brachial artery blood pressure (MAP) were measured continuously. Forearm vascular conductance (FVC, FBF ÷ MAP) was curve-fit with a monoexponential model, and vasodilation onset kinetics were assessed by mean response time (MRT, time to achieve 63% of steady state). SDF had no effect on MRT ( P = 0.90). NOS inhibition increased MRT ( P = 0.01). MRT during SDF+l-NMMA was not different from control exercise ( P = 0.76). PDE-5 inhibition alone has no effect on rapid-onset vasodilation. Whereas NOS inhibition decelerates vasodilator kinetics, when combined with SDF, vasodilator kinetics do not differ from control. These data suggest NO-independent activation of cGMP occurs at exercise onset; thus PDE-5 inhibition may improve vasodilation in pathologies where NO bioavailability is impaired. NEW & NOTEWORTHY We show that when NO bioavailability is reduced, PDE-5 inhibition can restore vasodilation onset kinetics of exercise-mediated vasodilation via NO-independent cGMP pathways. These data suggest PDE-5 inhibition may improve exercise vasodilation onset kinetics in pathologies where NO bioavailability is impaired.
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Kellawan et al. (2017) studied Healthy adults (n=29). Sildenafil citrate and/or l-NMMA vs. Control conditions was evaluated on Vasodilation onset kinetics assessed by mean response time (MRT) (p=0.90 for SDF, 0.01 for l-NMMA, 0.76 for SDF+l-NMMA). NOS inhibition decelerated exercise-onset vasodilator kinetics (P=0.01), but concurrent PDE-5 inhibition with sildenafil restored kinetics to control levels (P=0.76).
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