The Role of Nitric Oxide in Regulating Microvascular Oxygen Pressure During Diaphragm Contraction in Rats

The diaphragm muscle is the primary muscle involved in inspiration and is unique to mammals. Because the diaphragm is a constantly active muscle, its contraction may depend on oxidative phosphorylation and O₂ supply to create adenosine triphosphate. This study aimed to evaluate the role of intrinsic vasodilator nitric oxide (NO) in diaphragm O₂ dynamics.

Wistar male rats (n = 6, 10 wks old, 311 ± 14 g) were mechanically ventilated under isoflurane anesthesia. The diaphragm was exposed to measure microvascular partial O₂ pressure (PO₂mv) by phosphorescence quenching technique during electrical stimulation-induced diaphragm contractions (6 V, 2 ms, 2 Hz, 180 s). The 180 s of muscle contractions and PO₂mv measurement were repeated 10 min after endothelial NO synthase inhibition by the intra-arterial infusion of nitro-l-arginine methyl ester (L-NAME; eNOS inhibitor). The PO₂mv change during the transition from rest to contraction was fitted to a nonlinear regression model. Time delay, time constant (tau), rate constant (K), and nadir in PO₂mv were calculated and compared before and after eNOS inhibition. [Results] Diaphragm PO₂mv decreased during contractions both before and after eNOS inhibition. The time delay and K were not different before and after L-NAME. However, the L-NAME administration decreased the tau and nadir in PO₂mv (tau, 7.61 [5.18-13.41] vs. 3.36 [1.81-5.57] s; nadir, 7.45 [1.41-14.85] vs. 3.93 [0.89-9.47] mmHg; before vs. after eNOS inhibition, median [25-75 percentiles], P < 0.05, respectively).

The time constant in PO₂mv is determined by oxygen supply to the capillaries and oxygen utilization. The faster time constant and lower nadir in PO₂mv possibly indicate the slower and lower oxygen supply to diaphragm capillaries after eNOS inhibition.

The NO has a crucial role in the diaphragm oxygen dynamics of intact rats.