Phosphodiesterase-5 inhibition preserves exercise onset vasodilator kinetics when NOS activity is reduced

BBackground: 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), 2) decelerated during NO synthase inhibition (L-N^G-monomethyl arginine, L-NMMA), 3) effect of SDF on vasodilation onset kinetics would be attenuated with concurrent L-NMMA. Methods: 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) was 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). Results: 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). Conclusion: 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.

from Physiology via xlomafota13 on Inoreader http://ift.tt/2gfOOhw
via IFTTT