Effects of acute phosphodiesterase type 5 inhibition on skeletal muscle interstitial PO2 during contractions and recovery

Abstract

The oxygen partial pressure within the interstitial space (PO₂is; 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 PO₂is during muscle metabolic transitions, thereby slowing PO₂is on- and accelerating PO₂is off-kinetics. The rat spinotrapezius muscle (n = 17) was exposed for PO₂is 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 PO₂is (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 PO₂is (17.7 ± 1.6) compared to CON (12.8 ± 0.9) and SIL1 (13.4 ± 0.8) (p < 0.05). The overall PO₂is response during recovery (i.e., area under the PO₂is 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 PO₂is response during contractions or recovery (p > 0.05). However, sildenafil lowered MAP and improved skeletal muscle interstitial oxygenation in healthy rats. Specifically, SIL7 enhanced PO₂is at rest and during recovery from submaximal muscle contractions. Potentiation of the nitric oxide pathway with sildenafil enhances microvascular blood-myocyte O₂ transport and is expected to improve repeated bouts of contractile activity.