Effects of acute phosphodiesterase type 5 inhibition on skeletal muscle interstitial PO during contractions and recovery.

The oxygen partial pressure within the interstitial space (POis; mmHg) provides the driving force for oxygen diffusion into the myocyte thereby supporting oxidative phosphorylation. We tested the hypothesis that potentiation of the nitric oxide pathway with sildenafil (phosphodiesterase type 5 inhibitor) would enhance POis during muscle metabolic transitions, thereby slowing POis on- and accelerating POis off-kinetics. The rat spinotrapezius muscle (n = 17) was exposed for POis measurements via phosphorescence quenching under control (CON), low-dose sildenafil (1 mg/kg i.a., SIL1) and high-dose sildenafil (7 mg/kg i.a., SIL7). Data were collected at rest and during submaximal twitch contractions (1 Hz, 4-6 V, 3 min) and recovery (3 min). Mean arterial blood pressure (MAP; mmHg) was reduced with both SIL1 (pre:132 ± 5; post:99 ± 5) and SIL7 (pre:111 ± 6; post:99 ± 4) (p < 0.05). SIL7 elevated resting POis (18.4 ± 1.1) relative to both CON (15.7 ± 0.7) and SIL1 (15.2 ± 0.7) (p < 0.05). In addition, SIL7 increased end-recovery POis (17.7 ± 1.6) compared to CON (12.8 ± 0.9) and SIL1 (13.4 ± 0.8) (p < 0.05). The overall POis response during recovery (i.e., area under the POis curve) was greater in SIL7 (4107 ± 444) compared to CON (3493 ± 222) and SIL1 (3114 ± 205 mmHg s) (p < 0.05). Contrary to our hypothesis, there was no impact of acute SIL (1 or 7 mg/kg) on the speed of the POis response during contractions or recovery (p > 0.05). However, sildenafil lowered MAP and improved skeletal muscle interstitial oxygenation in healthy rats. Specifically, SIL7 enhanced POis at rest and during recovery from submaximal muscle contractions. Potentiation of the nitric oxide pathway with sildenafil enhances microvascular blood-myocyte O transport and is expected to improve repeated bouts of contractile activity.